Meropenem-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in a patient with known type IV penicillin hypersensitivity.

BMJ Case Rep. 2019 Aug 20;12(8):

Authors: Sameed M, Nwaiser C, Bhandari P, Schmalzle SA

Abstract
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered variants of a disease continuum that results in a life-threatening exfoliative mucocutaneous disease. These are categorised as type IV cell-mediated delayed hypersensitivity reactions, and antibiotics are often implicated as a cause. Penicillins and other beta-lactam antibiotics are known to cause both immediate and delayed hypersensitivity reactions. While immediate IgE-mediated cross-reactivity between penicillins and carbapenems is well studied, less information on the risk of type IV delayed cell-mediated cross-reactivity between the two is available. We present a case of meropenem-induced SJS in a patient with documented history of SJS from amoxicillin. There are few cases of cross-reactivity with carbapenems reported in the literature, but based on the potential for life-threatening reaction, it is likely prudent to avoid the use of any beta-lactams in a patient with a history of SJS, TEN or any other severe cutaneous adverse reactions to another beta-lactam antibiotic.

PMID: 31434673 [PubMed - indexed for MEDLINE]

[Risk of medicines in pregnancy: a problem of knowledge transfer with ethical implications].

Cuad Bioet. 2019 May-Aug;30(99):199-207

Authors: Alegre-Del Rey EJ, Fénix-Caballero S, Díaz-Navarro J

Abstract
Drug use in pregnancy is essential and beneficial, but it is needed to check their safety. Available scientific evidence is poor and difficult to interpret. Risk classifications (FDA, ADEC) have shown to be too simple and categorical; they lead to inaccurate perceptions of risk and unfortunate decisions, such as interrumption of medication, or abortion. This has become clear with antidepressants or the antiretroviral efavirenz. Although abortion is not justified, misinformation contributes even more to the problem. Information tends to obviate that not every risk in pregnancy is teratogenic, that the existence of risk does not imply high probability, and that the nature and probability of the risk vary according to the stage.

PMID: 31206299 [PubMed - indexed for MEDLINE]

Assessment of the benefit-risk balance of SGLT2 inhibitors: Commentary on a new 'French paradox'.

Diabetes Metab. 2019 09;45(4):319-321

Authors: Scheen AJ, Darmon P, Hanaire H, writing committee of the position statement by the French-Speaking Society of Diabetes (SFD)

PMID: 31005757 [PubMed - indexed for MEDLINE]

Incidence of adverse events associated with technical care and support in French nursing homes: the EHPAGE project.

Geriatr Psychol Neuropsychiatr Vieil. 2019 Sep 01;17(3):243-253

Authors: Teigné D, Mouret D, Lucas M, Gaultier A, Moret L, Leclère B, Terrien N

Abstract
A rise in the number of dependent elderly people has made nursing homes an important part of the French health system. Through the struggle against adverse events associated with treatments, the question of the residents' safety and wellbeing has been paramount. To get an estimation of the highest incidence rates of adverse events in nursing homes, we carried out a follow-up study on 536 residents over 15-day periods between November 2016 and May 2017 in 8 French nursing homes. Notifications by professionals coupled with explorations by an investigating physician helped evidence the different typologies and degrees of seriousness of treatment-related adverse events. The 149 treatment-related adverse events that were identified belonged to 13 risk domains. Four of these domains accounted for 60% of treatment-related adverse events: 'medication and medical provision', 'living environment', 'technical care and accompaniment', 'care organization and coordination'. Four treatment-related adverse events out of the 149 (2.7%) had a level of seriousness rated as 4; 16 (10.7%) had a seriousness level rated as 3. Finally, particular attention should be paid to suicide risk. These first results need to be corroborated, but they will help develop messages of prevention aimed at professionals.

PMID: 30907362 [PubMed - indexed for MEDLINE]

Antimicrobial-associated harm in critical care: a narrative review.

Intensive Care Med. 2020 Jan 29;:

Authors: Arulkumaran N, Routledge M, Schlebusch S, Lipman J, Conway Morris A

Abstract
The belief that, for the individual patient, the benefit of prompt and continued use of antimicrobials outweighs any potential harm is a significant barrier to improved stewardship of these vital agents. Antimicrobial stewardship may be perceived as utilitarian rationing, seeking to preserve the availability of effective antimicrobials by limiting the development of resistance in a manner which could conflict with the immediate treatment of the patient in need. This view does not account for the growing evidence of antimicrobial-associated harm to individual patients. This review sets out the evidence for antimicrobial-associated harm and how this should be balanced with the need for prompt and appropriate therapy in infection. It describes the mechanisms by which antimicrobials may harm patients including: mitochondrial toxicity; immune cell toxicity; adverse drug reactions; selection of resistant organisms within a given patient; and disruption of the microbiome. Finally, the article indicates how the harms of antimicrobials may be mitigated and identifies areas for research and development in this field.

PMID: 31996961 [PubMed - as supplied by publisher]

New medication adverse reaction education.

Nurs Manage. 2019 Nov;50(11):33-37

Authors: Price JB

Abstract
Increasing patient satisfaction scores.

PMID: 31688544 [PubMed - indexed for MEDLINE]

Development of a mortality score to assess risk of adverse drug reactions among hospitalized patients with moderate to severe chronic kidney disease.

BMC Pharmacol Toxicol. 2019 07 08;20(1):41

Authors: Danial M, Hassali MA, Meng OL, Kin YC, Khan AH

Abstract
BACKGROUND: Chronic kidney disease (CKD) is a significant health burden that increases the risk of adverse events. Currently, there is no validated models to predict risk of mortality among CKD patients experienced adverse drug reactions (ADRs) during hospitalization. This study aimed to develop a mortality risk prediction model among hospitalized CKD patients whom experienced ADRs.
METHODS: Patients data with CKD stages 3-5 admitted at various wards were included in the model development. The data collected included demographic characteristics, comorbid conditions, laboratory tests and types of medicines taken. Sequential series of logistic regression models using mortality as the dependent variable were developed. Bootstrapping method was used to evaluate the model's internal validation. Variables odd ratio (OR) of the best model were used to calculate the predictive capacity of the risk scores using the area under the curve (AUC).
RESULTS: The best prediction model included comorbidities heart disease, dyslipidaemia and electrolyte imbalance; psychotic agents; creatinine kinase; number of total medication use; and conservative management (Hosmer and Lemeshow test =0.643). Model performance was relatively modest (R square = 0.399) and AUC which determines the risk score's ability to predict mortality associated with ADRs was 0.789 (95% CI, 0.700-0.878). Creatinine kinase, followed by psychotic agents and electrolyte disorder, was most strongly associated with mortality after ADRs during hospitalization. This model correctly predicts 71.4% of all mortality pertaining to ADRs (sensitivity) and with specificity of 77.3%.
CONCLUSION: Mortality prediction model among hospitalized stages 3 to 5 CKD patients experienced ADR was developed in this study. This prediction model adds new knowledge to the healthcare system despite its modest performance coupled with its high sensitivity and specificity. This tool is clinically useful and effective in identifying potential CKD patients at high risk of ADR-related mortality during hospitalization using routinely performed clinical data.

PMID: 31287030 [PubMed - indexed for MEDLINE]

Countrywide prevalence of critical drug interactions in Hungarian outpatients: a retrospective analysis of pharmacy dispensing data.

BMC Pharmacol Toxicol. 2019 05 31;20(1):36

Authors: Somogyi-Végh A, Ludányi Z, Erdős Á, Botz L

Abstract
BACKGROUND: Drug-drug interactions (DDIs) present a significant source of adverse drug reactions. Despite being one of the commonly cited risks to patient safety, prevention of DDIs still poses a challenge to healthcare systems. The prevalence of DDIs can be used as a quality indicator for the safety of prescribing. With the analysis of drug utilization databases, real-world data on critical DDIs can be obtained. The aim of this study was to establish a list of critical DDIs and estimate their prevalence in the Hungarian outpatient population.
METHODS: Since there is no conclusive and generally accepted repository of high-risk DDIs, a systematic search of the literature for consensus-based lists was performed. Based on these results and their analysis with 5 interaction compendia, we propose a simple methodology to identify critical combinations. Present study focused on DDIs which are (1) of high clinical importance thus being most likely to cause significant harm if not detected, (2) well-supported by available evidence and (3) affect drugs which are routinely dispensed in the community pharmacy setting. A retrospective analysis of prescriptions filled between 2013 and 2016 was performed. The source of drug utilization data was the IQVIA's national prescription fill database. The number of interacting drug pairs dispensed at the same time to the same patient was established.
RESULTS: After excluding drugs with low dispensing rates, the analysis covered 39 DDIs. The distribution of risk categories of the analysed DDIs was inconsistent among different drug interaction compendia. The total number of prescriptions filled varied between 173924449 and 176368468 per year. The prevalence of the selected potential DDIs ranged from 0.00 to 355.89 per 100000 prescriptions per year. There was significant variation between how the number of cases had changed for each DDI throughout the study period, no general tendency could have been described.
CONCLUSIONS: There were 1.8 million cases of co-dispensing each year, where prescribers' and community pharmacists' role in recognizing and managing potentially serious interactions was or would have been critical. The method presented to identify high-risk DDIs can serve as a starting point for the much-needed improvement of routine interaction screening.

PMID: 31151485 [PubMed - indexed for MEDLINE]

Nature and prevalence of adverse drug reaction of antiretroviral medications in Halibet National Referral Hospital: a retrospective study.

BMC Pharmacol Toxicol. 2019 05 06;20(1):24

Authors: Hagos L, Fessehaye S, Anand IS

Abstract
BACKGROUND: Monitoring the safety of antiretroviral therapy (ART) remains a challenge in resource-constrained countries such as Eritrea due to their serious adverse drug reactions (ADRs). This study was aimed at assessing the prevalence, nature, seriousness and possible risk factors of ART associated ADRs in Halibet National Referral Hospital in Eritrea.
METHOD: A three month retrospective, longitudinal, descriptive study of patients treated with ART between September 2005 and December 2016 was conducted in Halibet National Referral Hospital. Demographic characteristics, treatment details, reaction and outcome details, laboratory investigations and other information was abstracted manually from patients' clinical cards. Statistical analysis was conducted using both univariate and multivariate analysis and statistical significance was tested using 95% confidence intervals and/or p-value. A P-value < 0.05 was regarded as being statistically significant.
RESULTS: Of the 309 patients screened, 62.8% encountered at least one ADR and 29.8% of the reactions were serious with similar male to female ratio. Gastrointestinal symptoms were the most common ADR and were associated mostly with Atripla followed by AZT + 3TC + NVP drug combinations, but lipodystrophy followed by peripheral neuropathy which were both commonly associated with Stavudine and anemia associated with Zidovudine were the most serious. Patients with CD4 count below 200 were more likely to develop ADRs (p = 0.000).
CONCLUSION: ADRs associated with ART drugs in Halibet hospital were found to be highly prevalent. Furthermore, CD4 count below 200, was identified as a major risk factor that predisposes patients to ADRs. This is burdensome to resource constrained countries such as Eritrea who have limited drug options and high HIV prevalence, therefore these findings will help patients and healthcare professionals understand the nature as well as seriousness of these ADRs and identify the risks involved with ART medications which can help minimize ART associated ADRs early on.

PMID: 31060603 [PubMed - indexed for MEDLINE]

Characterization and preventability of adverse drug events as cause of emergency department visits: a prospective 1-year observational study.

BMC Pharmacol Toxicol. 2019 04 27;20(1):21

Authors: Lo Giudice I, Mocciaro E, Giardina C, Barbieri MA, Cicala G, Gioffrè-Florio M, Carpinteri G, Di Grande A, Spina E, Arcoraci V, Cutroneo PM

Abstract
BACKGROUND: Adverse drug events (ADEs) are a significant cause of emergency department (ED) visits, with a major impact on healthcare resource utilization. A multicentre observational study, aimed to describe frequency, seriousness and preventability of ADEs reported in four EDs, was performed in Sicily (Italy) over a 1-year period.
METHODS: Two trained monitors for each ED supported clinicians in identifying ADEs of patients admitted to EDs between June 1st, 2013 and May 31st, 2014 through a systematic interview of patients or their caregivers and with an additional record review. A research team analyzed each case of suspected ADE, to make a causality assessment applying the Naranjo algorithm and a preventability assessment using Schumock and Thornton criteria. Absolute and percentage frequencies with 95% confidence interval (CI) and medians with interquartile ranges (IQR) were estimated. Logistic regression models were used to evaluate independent predictors of serious and certainly preventable ADEs.
RESULTS: Out of 16,963 ED visits, 575 (3.4%) were associated to ADEs, of which 15.1% resulted in hospitalization. ADEs were classified as probable in 45.9%, possible in 51.7% and definite in 2.4% of the cases. Moreover, ADEs were considered certainly preventable in 12.3%, probably preventable in 58.4%, and not preventable in 29.2% of the cases. Polytherapy influenced the risk to experience a serious, as well as a certainly preventable ADE. Whilst, older age resulted an independent predictor only of serious events. The most common implicated drug classes were antibiotics (34.4%) and anti-inflammatory drugs (22.6%). ADEs due to psycholeptics and antiepileptics resulted preventable in 62.7 and 54.5% of the cases, respectively. Allergic reactions (64%) were the most frequent cause of ADE-related ED visits, followed by neurological effects (10.2%) that resulted preventable in 1.9 and 37.3% of the cases, respectively.
CONCLUSION: ADEs are a frequent cause of ED visits. The commonly used antibiotics and anti-inflammatory drugs should be carefully managed, as they are widely involved in mild to severe ADEs. Polytherapy is associated with the occurrence of serious, as well as certainly preventable ADEs, while older age only with serious events. A greater sensitivity to drug monitoring programs among health professionals is needed.

PMID: 31029178 [PubMed - indexed for MEDLINE]

Ascertainment of Aspirin Exposure Using Structured and Unstructured Large-scale Electronic Health Record Data.

Med Care. 2019 10;57(10):e60-e64

Authors: Bustamante R, Earles A, Murphy JD, Bryant AK, Patterson OV, Gawron AJ, Kaltenbach T, Whooley MA, Fisher DA, Saini SD, Gupta S, Liu L

Abstract
BACKGROUND: Aspirin impacts risk for important outcomes such as cancer, cardiovascular disease, and gastrointestinal bleeding. However, ascertaining exposure to medications available both by prescription and over-the-counter such as aspirin for research and quality improvement purposes is a challenge.
OBJECTIVES: Develop and validate a strategy for ascertaining aspirin exposure, utilizing a combination of structured and unstructured data.
RESEARCH DESIGN: This is a retrospective cohort study.
SUBJECTS: In total, 1,869,439 Veterans who underwent usual care colonoscopy 1999-2014 within the Department of Veterans Affairs.
MEASURES: Aspirin exposure and dose were obtained from an ascertainment strategy combining query of structured medication records available in electronic health record databases and unstructured data extracted from free-text progress notes. Prevalence of any aspirin exposure and dose-specific exposure were estimated. Positive predictive value and negative predictive value were used to assess strategy performance, using manual chart review as the reference standard.
RESULTS: Our combined strategy for ascertaining aspirin exposure using structured and unstructured data reached a positive predictive value and negative predictive value of 99.2% and 97.5% for any exposure, and 92.6% and 98.3% for dose-specific exposure. Estimated prevalence of any aspirin exposure was 36.3% (95% confidence interval: 36.2%-36.4%) and dose-specific exposure was 35.4% (95% confidence interval: 35.3%-35.5%).
CONCLUSIONS: A readily accessible approach utilizing a combination of structured medication records and query of unstructured data can be used to ascertain aspirin exposure when manual chart review is impractical.

PMID: 30807451 [PubMed - indexed for MEDLINE]

Derivation and Validation of a Major Toxicity Risk Score Among Nonsteroidal Antiinflammatory Drug Users Based on Data From a Randomized Controlled Trial.

Arthritis Rheumatol. 2019 08;71(8):1225-1231

Authors: Solomon DH, Shao M, Wolski K, Nissen S, Husni ME, Paynter N

Abstract
OBJECTIVE: While nonsteroidal antiinflammatory drugs (NSAIDs) are commonly used in rheumatology, they can cause major toxicity. Improving the risk/benefit ratio requires a more precise understanding of risk. This study was undertaken to derive and validate a risk score for major toxicity among NSAID users enrolled in a randomized controlled trial.
METHODS: Patients enrolled in a randomized controlled trial who had known cardiovascular disease or risk factors as well as osteoarthritis or rheumatoid arthritis were divided into derivation and validation cohorts. Patients were randomized to receive celecoxib, naproxen, or ibuprofen at typical dosages. The risk score was designed to predict the 1-year occurrence of major toxicity among NSAID users, including major adverse cardiovascular events, acute kidney injury, significant gastrointestinal events, and mortality. Variables significantly associated with major toxicity were candidates for inclusion in the final regression model. After derived models were found to have a similar model fit in the validation set, the cohorts were combined, allowing calculation of a risk score.
RESULTS: In the derivation cohort, significant variables included age, male sex, history of cardiovascular disease, hypertension, diabetes mellitus, tobacco use, statin use, elevated serum creatinine level, hematocrit level, and type of arthritis. The C-index was 0.73 in the validation cohort and 0.71 in the total cohort; the model was well calibrated. Of the total population with complete data (n = 23,735), 1,080 participants (4.6%) had a predicted 1-year risk of major toxicity of <1%, 16,273 (68.6%) had a predicted risk of 1-4%, and 6,382 (26.9%) had a predicted risk of >4%.
CONCLUSION: The risk score accurately categorizes the 1-year risk of major toxicity among NSAID users and may be useful in identifying patients who can safely use these agents.

PMID: 30801994 [PubMed - indexed for MEDLINE]

Novel Genetic Risk Variants Can Predict Anti-TNF Agent Response in Patients With Inflammatory Bowel Disease.

J Crohns Colitis. 2019 Aug 14;13(8):1036-1043

Authors: Wang MH, Friton JJ, Raffals LE, Leighton JA, Pasha SF, Picco MF, Cushing KC, Monroe K, Nix BD, Newberry RD, Faubion WA

Abstract
BACKGROUND: It is important to identify patients with inflammatory bowel disease [IBD] refractory to anti-tumour necrosis factor [TNF] therapy, to avoid potential adverse effects and to adopt different treatment strategies. We aimed to identify and validate clinical and genetic factors to predict anti-TNF response in patients with IBD.
MATERIALS AND METHODS: Mayo Clinic and Washington University IBD genetic association study cohorts were used as discovery and replicate datasets, respectively. Clinical factors included sex, age at diagnosis, disease duration and phenotype, disease location, bowel resection, tobacco use, family history of IBD, extraintestinal manifestations, and response to anti-TNF therapy.
RESULTS: Of 474 patients with IBD treated with anti-TNF therapy, 41 [8.7%] were refractory to therapy and 433 [91.3%] had response. Multivariate analysis showed history of immunomodulator use (odds ratio 10.2, p = 8.73E-4) and bowel resection (odds ratio 3.24, p = 4.38E-4) were associated with refractory response to anti-TNF agents. Among genetic loci, two [rs116724455 in TNFSF4/18, rs2228416 in PLIN2] were successfully replicated and another four [rs762787, rs9572250, rs144256942, rs523781] with suggestive evidence were found. An exploratory risk model predictability [area under the curve] increased from 0.72 [clinical predictors] to 0.89 after adding genetic predictors. Through identified clinical and genetic predictors, we constructed a preliminary anti-TNF refractory score to differentiate anti-TNF non-responders (mean [standard deviation] score, 5.49 [0.99]) from responders (2.65 [0.39]; p = 4.33E-23).
CONCLUSIONS: Novel and validated genetic loci, including variants in TNFSF, were found associated with anti-TNF response in patients with IBD. Future validation of the exploratory risk model in a large prospective cohort is warranted.

PMID: 30689765 [PubMed - indexed for MEDLINE]

Outwitting an old neglected nemesis: A review on leveraging integrated data-driven approaches to aid in unraveling of leishmanicides of therapeutic potential.

Curr Top Med Chem. 2020 Jan 28;:

Authors: Kwofie SK, Broni E, Dankwa B, Enninful KS, Kwarko GB, Darko L, Durvasula R, Kempaiah P, Rath B, Miller Iii WA, Yaya A, Wilson MD

Abstract
The global prevalence of leishmaniasis has increased with skyrocketed mortality in the past decade. The causative agent of leishmaniasis is leishmania species, which infects populations in almost all the continents. Prevailing treatment regimens are consistently inefficient with reported side effects, toxicity and drug resistance. This review complements existing ones by discussing current state of treatment options, therapeutic bottlenecks including chemoresistance and toxicity, as well as drug targets. It further highlights innovative applications of nanotherapeutics-based formulations, inhibitory potential of leishmanicides, anti-microbial peptides and organometallic compounds on leishmanial species. Moreover, it provides essential insights into recent machine learning-based models which have been used to predict novel leishmanicides and also discusses other new models which could be adopted to develop fast, efficient, robust and novel algorithms to aid in unraveling the next generation of anti-leishmanial drugs. A plethora of enriched functional genomic, proteomic, structural biology, high throughput bioassay and drug related datasets are currently warehoused in both general and leishmania-specific databases. The warehoused datasets are essential inputs for training and testing algorithms to augment prediction of biotherapeutic entities. In addition, we demonstrate how pharmacoinformatics techniques including ligand-, structure- and pharmacophore-based virtual screening approaches have been utilized to screen ligand libraries against both modeled and experimentally solved 3D structures of essential drug targets. In the era of data-driven decision-making, we believe that highlighting intricately linked topical issues relevant to leishmanial drug discovery offers a one-stop-shop opportunity to decipher critical literature with potential to unlock implicit breakthroughs.

PMID: 31994465 [PubMed - as supplied by publisher]

Prevalence of methotrexate intolerance among patients with rheumatoid arthritis using the Arabic version of the methotrexate intolerance severity score.

Int J Rheum Dis. 2019 Aug;22(8):1572-1577

Authors: Albaqami J, Alshalhoub R, Almalag H, Dessougi M, Al Harthi A, Bedaiwi MK, Omair MA

Abstract
AIM: Methotrexate (MTX) is the anchor drug for the treatment of rheumatoid arthritis (RA). MTX is associated with adverse events that limit its use. The MTX intolerance severity score (MISS) was developed to identify symptoms related to MTX use in juvenile idiopathic arthritis and RA patients. The aim of this study is to translate and validate the MISS in the Arabic language.
METHODS: Forward and backward translation of the MISS were performed by two fluent Arabic translators and reviewed by three rheumatologists. Consecutive patients with RA who used MTX for ≥3 months were recruited from two tertiary care centers in Riyadh, Saudi Arabia. A test was considered positive if the patient scored ≥6 points. The internal consistency and stability of the items were evaluated using Cronbach's alpha and the test-retest method.
RESULTS: A total of 185 patients were recruited. Of those patients, 158 (85.4%) were female. The mean (±SD) age and disease duration were 49.7 (±12.67) and 8.67 (±7.1) years, respectively. The mean Disease Activity Score of 28 joints was 3.2 (±1.3). Fifty-five (30%) patients were illiterate. Seventy-three (39.5%) patients had a positive MISS. Of those patients, 55 (75.3%) and 18 (24.7%) were using the oral and subcutaneous forms of MTX, respectively. The Arabic MISS had good internal consistency (Cronbach's alpha = 0.792) and a factorable study size for test-retest and factor analysis (Kaiser-Meyer-Olkin = 0.745).
CONCLUSION: The Arabic MISS showed validity and good reliability in detecting MTX intolerance in RA patients. MTX intolerance is prevalent among RA patients. Larger studies are needed to confirm these findings.

PMID: 31245906 [PubMed - indexed for MEDLINE]

Association of Stevens-Johnson syndrome and toxic epidermal necrolysis with antiepileptic drugs in pediatric patients: Subgroup analysis based on a Japanese spontaneous database.

J Clin Pharm Ther. 2019 Oct;44(5):775-779

Authors: Inada A, Oyama S, Niinomi I, Wakabayashi T, Iwanaga K, Hosohata K

Abstract
WHAT IS KNOWN AND OBJECTIVE: Antiepileptic drugs (AEDs) are known to cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are severe cutaneous disorders; however, real-world data remain limited, especially on pediatric patients. The objective of this study was to investigate the association of AEDs with SJS and TEN in pediatric patients based on the Japanese Adverse Drug Event Report (JADER) database, which is a spontaneous reporting database.
METHODS: Adverse event reports submitted to the JADER database between 2004 and 2017 were analysed. We performed a retrospective pharmacovigilance disproportionality analysis, calculating the reporting odds ratio (ROR) with a 95% confidence interval (CI).
RESULTS AND DISCUSSION: A total of 159 605 adverse events were reported in pediatric patients. Significant SJS signals were detected for ethosuximide, phenytoin, phenobarbital, gabapentin, carbamazepine, zonisamide, clonazepam and lamotrigine. TEN signals were detected for ethosuximide, phenytoin, phenobarbital, gabapentin, carbamazepine and zonisamide, but the signal was strongest for gabapentin (ROR, 24.76; 95% CI, 11.4-53.9).
WHAT IS NEW AND CONCLUSION: Severe cutaneous disorders were associated with multiple AEDs, but individual AEDs were associated with variable signals. These results may be useful for minimizing the risk of SJS or TEN during treatment of children with AEDs.

PMID: 31231846 [PubMed - indexed for MEDLINE]

A 'Natural' thyroid storm!

J Clin Pharm Ther. 2019 Oct;44(5):813-814

Authors: Mohebbi MR, Chen AT

Abstract
WHAT IS KNOWN AND OBJECTIVE: Over the counter supplements are often taken for granted during medication reconciliation in the emergency department. Supplements are not regulated by FDA, and some can be potentially dangerous.
CASE SUMMARY: We report a case of thyrotoxicosis secondary to over the counter bovine thyroid supplements. Our patient presented with atrial fibrillation with rapid ventricular response refractory to calcium channel blockers. Had we not known about the supplement, the course of treatment would have been different with potential adverse outcome.
WHAT IS NEW AND CONCLUSION: Natural thyroid supplements are marketed as over the counter products and are largely unregulated. Thyroid extracts have been found to have disparaging inconsistencies in composition, delivering anywhere from non-existent to supratherapeutic doses. Thyroid supplements should be regulated considering the potential side effects.

PMID: 31211437 [PubMed - indexed for MEDLINE]

Clinically relevant drug-drug interactions and the risk for drug adverse effects among home-dwelling older persons with and without type 2 diabetes.

J Clin Pharm Ther. 2019 Oct;44(5):735-741

Authors: Ikäheimo I, Karjalainen M, Tiihonen M, Haanpää M, Kautiainen H, Saltevo J, Mäntyselkä P

Abstract
WHAT IS KNOWN AND OBJECTIVE: Polypharmacy and age are known to increase the risk for potential drug interactions. Type 2 diabetes has been associated with polypharmacy and several comorbidities. Currently, there is no information on whether the frequency of clinically relevant drug-drug interactions and the risk for drug adverse effects differ between older persons with and without diabetes. The aim of this study was to investigate the frequency of drug-drug interactions and the risk for drug adverse effects in these two groups in primary care.
METHODS: The basic study population consisted of Finnish home-dwelling primary care patients aged ≥ 65 years (N = 3039). For each person with diabetes, two controls were selected with adjusted age and gender. To collect data, electronic primary care patient records, a structured health questionnaire and a structured health examination conducted by a physician were utilized. Using the SFINX-PHARAO® database, drug-drug interactions and the risk for drug adverse effects were evaluated in 182 persons with type 2 diabetes and 176 persons without diabetes.
RESULTS AND DISCUSSION: There were no significant differences in the frequency of drug-drug interactions or the risk for drug adverse effects in persons with and without diabetes. At least one clinically relevant interaction was found in 81 (44.5%) persons with diabetes and 73 (41.5%) persons without diabetes. The most common drugs causing interactions included non-steroidal anti-inflammatory drugs (NSAIDs) and warfarin.
WHAT IS NEW AND CONCLUSION: There is no difference in the frequency of drug-drug interactions or risk for drug adverse effects in older home-dwelling persons with and without diabetes. Due to common comorbidities and commonly used drugs among persons with diabetes, drug-drug interactions involving warfarin or NSAIDs in particular should be carefully monitored to avoid drug adverse effects.

PMID: 31119771 [PubMed - indexed for MEDLINE]

Pharmacokinetics of isoniazid: The good, the bad, and the alternatives.

Tuberculosis (Edinb). 2019 05;116S:S66-S70

Authors: Erwin ER, Addison AP, John SF, Olaleye OA, Rosell RC

Abstract
Although isoniazid (INH) has been successful in treating Tuberculosis (TB) since its introduction in 1952, there has been continual reports of drug-associated hepatotoxicity in TB patients. These toxic side effects may reveal more about the recipient of the drug, than the drug itself. A combination of pharmacogenetic and pharmacokinetic studies have identified polymorphisms within enzymes involved in INH metabolism and detoxification. These essential metabolic enzymes include N-acetyltransferase 2, Cytochrome P450 2E1, and glutathione S transferases. Different phenotypes of these enzymes can affect the rate of INH metabolism, resulting in production of hepatotoxic metabolites. This review is intended to elucidate the pharmacokinetics of INH by examining its Administration, Distribution, Metabolism, and Elimination, while suggesting potential alternatives within INH personalized treatment to help reduce hepatotoxicity.

PMID: 31076322 [PubMed - indexed for MEDLINE]

Workshop on the Italian Pharmacovigilance System in the International Context: Critical Issues and Perspectives.

Drug Saf. 2019 05;42(5):683-687

Authors: Sultana J, Moretti U, Addis A, Caduff P, Capuano A, Kant A, Laporte JR, Lindquist M, Raine J, Sartori D, Trifirò G, Tuccori M, Venegoni M, van Puijenbroek E, Leone R

PMID: 30565019 [PubMed - indexed for MEDLINE]