World Health Organization-Uppsala Monitoring Research Articles

Liver Injury in People With HIV on Antituberculosis and/or Antiretroviral Therapy-Assessing Causality Using the Updated Roussel Uclaf Causality Assessment Method.

We compared performance of the Roussel Uclaf Causality Assessment Method (RUCAM) with multidisciplinary expert panel review in identifying a drug-induced liver injury (DILI) due to antituberculosis therapy (ATT) and/or antiretroviral therapy (ART). Cases were drawn from a prospective registry of hospitalised adults with suspected DILI due to ATT and/or ART in Cape Town, South Africa. Participants had to fulfil American Thoracic Society criteria for ATT interruption (alanine transaminase [ALT] ≥5 times upper limit of normal [ULN]/ALT ≥3 times [ULN] and symptomatic). Causality assessment by expert panel review served as reference standard. The panel ranked potentially implicated drugs as certain, probable, possible or unlikely causes guided by World Health Organization Uppsala Monitoring Centre criteria. The RUCAM was performed for each potentially implicated drug. We calculated sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause for liver injury. We included 48 participants. All were people with HIV (PWH). Twenty-seven were on concomitant ART and ATT, with a median of six potentially hepatotoxic drugs per case. Sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause of liver injury compared with expert panel review was 7% and 100% respectively. Implicated drugs (times ranked probable/certain by panel) were isoniazid (18/0), pyrazinamide (17/0), rifampicin (15/1), efavirenz (6/4) and lopinavir/ritonavir (1/0). PWH with liver injury received multiple potentially implicated drugs, which may increase liver injury risk and complicate causality assessment. Compared with expert panel review, the RUCAM had low sensitivity in detecting probable or certain drug causes of liver injury.

Accuracy in patient-reported adverse drug reactions and their recognition: a mixed-methods study.

The causality assessment tool can be utilized to assist patients in identifying adverse drug reactions (ADRs). To evaluate the accuracy of the causality assessment tool for patients identifying ADRs compared to assessments made by pharmacists, and to explore how patients recall and recognize symptoms as ADRs. Mixed methods study consisting of self-administered questionnaires (phase 1) and semi-structured, face-to-face interviews (phase 2) with patients who had experienced ADRs in the past year at a tertiary care hospital in Thailand. Out of 769 questionnaires, 716 were returned and 622 of these were both valid and had at least one ADR (86.8%). Classification of patient-reported symptoms using the causality assessment tool found 12 (1.9%) highly-probable ADRs, 399 (64.1%) probable ADRs, 207 (33.3%) possible ADRs, and 4 (0.6%) that were not classified as ADRs. There was fair agreement between patient-assessed and pharmacist-assessed causality classifications using the Naranjo algorithm (K = 0.268) and the World Health Organization Uppsala Monitoring Centre (WHO-UMC) criteria (K = 0.373). The timing relationship between the occurrence of symptoms and administration of a suspected drug was the most frequently mentioned reason that patients gave for recalling and recognizing suspected ADRs. Promoting the causality assessment tool for use by patients in collaboration with healthcare professionals is likely to enhance patients' ability to correctly identify ADRs and ultimately contribute to increased medication safety.

Pharmacovigilance Study of Anticancer Drugs in a Tertiary Care Teaching Hospital in North India: A Retrospective Study.

Anticancer agents are responsible for a majority of adverse drug reactions (ADRs) in cancer patients. ADR reporting with anticancer drugs is very rare in India due to the lack of awareness and knowledge about the Pharmacovigilance Programme of India. Hence, this study was done to assess the pattern of ADRs with anticancer agents in cancer patients and to increase awareness about ADR monitoring among healthcare professionals. This is an observational, retrospectiveand non-interventional study conducted in an ADR monitoring centre (AMC) in Govt. Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, North India. Voluntarily reported ADR forms with anticancer drugs as suspected drugs over a period of seven years from January 2016 to December 2022 were analyzed. Various parameters were analyzed, which include demographic details of the patients, type of ADR, department reporting ADR and suspected drug. Causality assessment, severity assessment and preventability assessment were done according to the World Health Organization Uppsala Monitoring Centre (WHO-UMC) scale, modified Hartwig and Siegel scale and modified Schumock and Thornton scale, respectively. The maximum numbers of ADRs were reported in the age group of 41-60 years (68.29%) and in females (59.75%). The maximum number of ADRs was reported with the use of taxanes (docetaxel and paclitaxel) (24.39%), targeted drugs (geftinib, imatinib, bortezomib, bevacizumab, rituximab and pazopanib) (24.39%) and platinum co-ordination complexes (cisplatin, oxaliplatin and carboplatin) (17.07%). Majority of the ADRs reported were shivering and ADRs on the skin. Majority of the ADRs were probable (64.70%), mild in nature (85.29%), definitely preventable (45.58%) and probably preventable (45.58%). ADR monitoring is needed to increase the outcome of anticancer drug treatment in cancer patients. The quality of treatment in cancer patients can be improved through the timely management of these ADRs. It is a need of the present era to inform healthcare professionals about the Pharmacovigilance Programme to increase the reporting of ADRs due to anticancer drugs.

Coinfection with Strongyloides and SARS-CoV-2: A Systematic Review.

Treatments for COVID-19, including steroids, might exacerbate Strongyloides disease in patients with coinfection. We aimed to systematically review clinical and laboratory features of SARS-CoV-2 and Strongyloides coinfection, investigate possible interventions, assess outcomes, and identify research gaps requiring further attention. We searched two electronic databases, LitCOVID and WHO, up to August 2022, including SARS-CoV-2 and Strongyloides coinfection studies. We adapted the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment to evaluate if using corticosteroids or other immunosuppressive drugs in COVID-19 patients determined acute manifestations of strongyloidiasis. We included 16 studies reporting 25 cases of Strongyloides and SARS-CoV-2 coinfection: 4 with hyperinfection syndrome; 2 with disseminated strongyloidiasis; 3 with cutaneous reactivation of strongyloidiasis; 3 with isolated digestive symptoms; and 2 with solely eosinophilia, without clinical manifestations. Eleven patients were asymptomatic regarding strongyloidiasis. Eosinopenia or normal eosinophil count was reported in 58.3% of patients with Strongyloides reactivation. Steroids were given to 18/21 (85.7%) cases. A total of 4 patients (19.1%) received tocilizumab and/or Anakirna in addition to steroids. Moreover, 2 patients (9.5%) did not receive any COVID-19 treatment. The causal relationship between Strongyloides reactivation and COVID-19 treatments was considered certain (4% of cases), probable (20% of patients), and possible (20% of patients). For 8% of cases, it was considered unlikely that COVID-19 treatment was associated with strongyloidiasis reactivations; the relationship between the Strongyloides infection and administration of COVID-19 treatment was unassessable/unclassifiable in 48% of cases. Of 13 assessable cases, 11 (84.6%) were considered to be causally associated with Strongyloides, ranging from certain to possible. Further research is needed to assess the frequency and risk of Strongyloides reactivation in SARS-CoV-2 infection. Our limited data using causality assessment supports recommendations that clinicians should screen and treat for Strongyloides infection in patients with coinfection who receive immunosuppressive COVID-19 therapies. In addition, the male gender and older age (over 50 years) may be predisposing factors for Strongyloides reactivation. Standardized guidelines should be developed for reporting future research.

Intensive care drug therapy and its potential adverse effects on blood pressure and heart rate in critically ill children

BackgroundOwing to complex treatment, critically ill children may experience alterations in their vital parameters. We investigated whether such hemodynamic alterations were temporally and causally related to drug therapy.MethodsIn a university pediatric intensive care unit, we retrospectively analyzed hemodynamic alterations defined as values exceeding the limits set for heart rate (HR) and blood pressure (BP). For causality assessment, we used the World Health Organization–Uppsala Monitoring Center (WHO–UMC) system, which categorizes the probability of causality as “certain,” “probable,” “possible,” and “unlikely.”ResultsOf 315 analyzed patients with 43,200 drug prescriptions, 59.7% experienced at least one hemodynamic alteration; 39.0% were affected by increased HR, 19.0% by decreased HR, 18.1% by increased BP, and 16.2% by decreased BP. According to drug information databases, 83.9% of administered drugs potentially lead to hemodynamic alterations. Overall, 88.3% of the observed hemodynamic alterations had a temporal relation to the administration of drugs; in 80.2%, more than one drug was involved. Based on the WHO–UMC system, a drug was rated as a “probable” causing factor for only 1.4% of hemodynamic alterations. For the remaining alterations, the probability ratings were lower because of multiple potential causes, e.g., several drugs.ConclusionsCritically ill children were frequently affected by hemodynamic alterations. The administration of drugs with potentially adverse effects on hemodynamic parameters is often temporally related to hemodynamic alterations. Hemodynamic alterations are often multifactorial, e.g., due to administering multiple drugs in rapid succession; thus, the influence of individual drugs cannot easily be captured with the WHO–UMC system.

Hydrocortisone-induced blood pressure reduction in a patient with anterior pituitary hypofunction: a case report

Hydrocortisone is widely used for the anti-inflammatory and immunosuppressive effects and physiological substitute of endogenous glucocorticoid. Allergic reaction to hydrocortisone is infrequent, but once it occurs, it can affect the...

A RETROSPECTIVE PHARMACOVIGILANCE ANALYSIS AT TERTIARY CARE HOSPITAL: AN OBSERVATIONAL STUDY

Objective: Pharmacovigilance Program of India is a robust program extending from government hospitals to non-government hospital for implementation of policy of safe and rational use of drugs and early signal generation for adverse effects of drugs. Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University is part of this program since 2004. Retrospective analysis of adverse drug reaction (ADR) reported to the adverse drug monitoring center at tertiary Care Hospital. Methods: The study site was Sir Sundar Lal Hospital, Institute of Medical Sciences Banaras Hindu University, Varanasi. The study was performed after the approval of the Institutional Ethics Committee, letter number: Dean/2020/EC/2153. It was a retrospective observational study. Data collected through VigiFlow software in standard IPC Pharmacovigilance Program of India prescribed suspected ADR form, from March 2020 to June 2021 were analyzed. Causality assessment was done using a World Health Organization Uppsala Monitoring Center scale. Results: In the present study, the percentage of male patients affected is 58% and 42% female patient got suffered from adverse drug effects. About 64% of adverse effect are in possible category followed by probable, that is, 36%. The majority of adverse effects are due to antimicrobials, that is, Cephalosporins and Antitubercular group of drugs. About 20.1% adverse events show gastrointestinal symptoms. In the present study, we also observed that 5.17% adverse effects are due to hydroxychloroquine account for gastritis, headache, lethargy, and vomiting which were prescribed as prophylactic drug for COVID-19. Conclusion: Medicine information OPD in every medical college is the need of the hour to increase awareness regarding adverse events. It is important to spread importance of reporting adverse events by spontaneous reporting under Pharmacovigilance Program of India to detect rare and unusual side effects.

Characteristics of adverse reactions among antipsychotic drugs using the Korean Adverse Event Reporting System database from 2010 to 2019.

Retrospective studies using spontaneous reporting system databases have provided a great understanding of adverse drug reactions (ADRs) in the real world, complementing the data obtained from randomized controlled trials. However, there have been few reports on large-scale epidemiological studies on the adverse effects of antipsychotics in Asia. This study aimed to investigate the characteristics of antipsychotic ADRs using a nationwide pharmacovigilance database. Data were collected from the Korea Adverse Event Reporting System database between 2010 and 2019. The study subjects were selected using the International Classification of Disease codes for diseases related to psychosis and Electronic Data Interchange codes for amisulpride, aripiprazole, clozapine, haloperidol, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. The causality assessment of "possible," "probable," or "certain" by the World Health Organization-Uppsala Monitoring Center System causality category was selected. All data were descriptively analyzed. In total, 5067 adverse events associated with antipsychotic drugs were reported. The antipsychotics that commonly resulted in ADRs were quetiapine (47.7%), olanzapine (11.3%), and clozapine (10.7%). Serious ADRs were most commonly observed with clozapine. Gastrointestinal and central nervous system problems occurred within a month when ADRs were classified according to the time of onset. In contrast, metabolic and bone marrow-related symptoms occurred after long-term use. Sedation and nausea were the most common ADRs in children and adolescents, whereas constipation and dizziness were common in adults and the elderly. This study extends our knowledge of antipsychotic ADRs in the Asian population.

Feature engineering and machine learning for causality assessment in pharmacovigilance: Lessons learned from application to the FDA Adverse Event Reporting System

BackgroundOur objective was to support the automated classification of Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) reports for their usefulness in assessing the possibility of a causal relationship between a drug product and an adverse event. MethodWe used a data set of 326 redacted FAERS reports that was previously annotated using a modified version of the World Health Organization–Uppsala Monitoring Centre criteria for drug causality assessment by a group of SEs at the FDA and supported a similar study on the classification of reports using supervised machine learning and text engineering methods. We explored many potential features, including the incorporation of natural language processing on report text and information from external data sources, for supervised learning and developed models for predicting the classification status of reports. We then evaluated the models on a larger data set of previously unseen reports. ResultsThe best-performing models achieved recall and F1 scores on both data sets above 0.80 for the identification of assessable reports (i.e. those containing enough information to make an informed causality assessment) and above 0.75 for the identification of reports meeting at least a Possible causality threshold. ConclusionsCausal inference from FAERS reports depends on many components with complex logical relationships that are yet to be made fully computable. Efforts focused on readily addressable tasks, such as quickly eliminating unassessable reports, fit naturally in SE's thought processes to provide real enhancements for FDA workflows.

An overview of the worldwide master key for pharmacovigilance and its role in India

Introduction: Pharmacovigilance (PV) is defined as the science and activities related to the detection, assessment, understanding, and prevention of Adverse Drug Reactions (ADRs) and related conditions.
 Methods: In the 1970s, several significant cases of ADR aided the advancement of the discipline. Between 1989 and 2004, several attempts were made to implement such a program in India, but the scheme was eventually launched in 2010 and is now operating successfully and producing positive results.
 Results: The pharmacovigilance Program of India (PvPI) contributed different data to the World Health Organization (WHO) Uppsala Monitoring Center (UMC) based on the data gathered from this process. Indian regulatory have sent several alerts to stakeholders and provided the Central Drugs Standard Control Organization (CDSCO) with several recommendations. CDSCO has since advised Marketing Authorisation Holders (MAHs) to follow the same guidelines and has amended the Drugs and Cosmetics Act and Regulations to reflect this.
 Conclusions: The time has come for Indian regulatory authorities to take the required action based on data generated in our country rather than data generated in several other countries.

Carbamazepine induced leukopenia: A case series

This is a case series of 4 patients who developed leukopenia on, controlled-release carbamazepine (CBZCR) monotherapy for focal seizure prophylaxis. All 4 cases (2 males and 2 females), presented to the neurology department with history of episodes of sudden onset, abnormal body movements. Patients were diagnosed as cases of focal seizures and were prescribed tablet CBZ-CR 300 mg twice a day for seizure prophylaxis. One month later patients presented for follow-up and were continuing with the treatment. Blood biochemistry parameters indicated leukopenia with total leukocyte count less than 4000 per mm3. According to World Health Organization Uppsala monitoring Centre (WHO-UMC) causality assessment, all 4 cases were classified as ‘probable/likely’ for carbamazepine-induced leukopenia. Carbamazepine was continued and total leukocyte count gradually recovered on 3-months follow-up. Conclusion: Total leukocyte count should be documented before initiating carbamazepine therapy. Patients with pre-existing leukopenia should not receive carbamazepine. All patients receiving carbamazepine should be monitored for leukocyte count in addition to other blood biochemistry parameters. Keywords: Carbamazepine,Drug induced leukopenia, Focal-seizure, Total leukocyte count.

Altered Behavior: An Infrequent Presentation with Levetiracetam

Levetiracetam has been associated with aggressive behavior and mania.We are reporting a case of agitation and aggressive behavior following levetiracetam monotherapy for focal seizure prophylaxis. A 48 years old man, who presented to the neurology department with history of four episodes of sudden onset abnormal body movements. Patient was diagnosed with focal seizures with secondary generalization and was prescribed tablet levetiracetam 500 mg twice a day for seizure prophylaxis. Three weeks later patient presented with complaints of excessive sleepiness during daytime, agitation and aggressive behavior, though seizure free. According to World Health Organization Uppsala monitoring Centre (WHO-UMC) causality assessment system the case was classified as probable/likely for levetiracetam-induced altered behavior. Levetiracetam was discontinued, and tablet carbamazepine controlled-release 300 mg twice daily was substituted. Within 2 days of switching therapy the agitation and aggression reduced substantially. Although levetiracetam has fewer side effects than traditional antiepileptic medications, but it is imperative to continuously monitor the patient for infrequent adverse effects also, so that required modifications to drug label may be done. Keywords: Aggression, Agitation, Altered behavior, Levetiracetam.

An Overview of World-Wide Master Key for Drug Safety Monitoring (Pharmacovigilance) and Its Role in India

Pharmacovigilance (PV) described as science & actions connecting to the identification, evaluation, awareness, & mitigation of Adverse Drug Reactions (ADRs) or associated conditions. Some serious cases of ADR contributed to the development of this discipline in the 1970s. There have been many efforts to establish such a programme in India between 1989-2004, but the system has finally begun in 2010 and is functioning successfully and achieving meaningful results. Based on the data gathered via this method, Pharmacovigilance Program of India (PvPI) contributed various data to the World Health Organization (WHO) Uppsala Monitoring Centre (UMC). They also issued some warnings to the stakeholder and made a range of suggestions to the Central Drugs Standard Control Organisation (CDSCO). CDSCO has also advised Marketing Permit Holders (MAHs) to comply with the same requirements and has introduced relevant changes to the Drugs and Cosmetics Act & Regulations. The time has arrived when Indian regulatory authorities would undertake the requisite action on the basis of data produced in our country rather than on the basis of data generated in several other countries

A STUDY OF AGREEMENT BETWEEN WHO-UPPSALA MONITORING CENTRE CRITERIA, NARANJO ALGORITHM, AND LIVERPOOL ALGORITHM FOR CAUSALITY ASSESSMENT OF ADVERSE DRUG REACTIONS

Objective: A standard causality assessment tool of an adverse drug reaction (ADR) is essential to compute the risk-benefit assessment of the medication taken by the patient and categorize its relationship likelihood. It should be reproducible and should not differ with the background and experience of the evaluator. Though there are a large number of causality assessment tools, none is unanimously accepted worldwide. So, this study was done to assess the agreement between three frequently used methods of causality assessment, the World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) system, the Naranjo’s algorithm, and the Liverpool algorithm.
 Methods: 172 ADR forms from the pharmacovigilance unit were randomly selected for the study. Causality assessment was done using three different methods, the WHO-UMC system, Naranjo’s algorithm, and the Liver pool algorithm. Cohen’s Kappa statistics was applied to look for agreement between the causality assessment methods.
 Results: The agreement between the WHO-UMC criteria and Naranjo’s algorithm was the highest (136), with a Kappa value of 0.511, suggesting a moderate level of agreement. A maximum number of disagreements were noted between the WHO-UMC system and the Liverpool algorithm method (110).
 Conclusion: A moderate agreement exists between the WHO-UMC system and the Naranjo algorithm. There is poor agreement between the Liverpool algorithm and the other two scales. Therefore, it is recommended that both the WHO-UMC system and the Naranjo algorithm be used for causality assessment of ADRs.

LEVETIRACETAM INDUCED URTICARIA IN PATIENT OF FOCAL SEIZURES; A CASE REPORT

Drug rash due to medications are common and can be serious leading to increase in morbidity and mortality. Drug rash can be caused by antiepileptic medications also. We are reporting a case of cutaneous reaction secondary to levetiracetam. A 22 years old female presented to the hospital with history of three episodes of seizures. She was diagnosed with focal seizures with secondary generalization and was prescribed tablet levetiracetam 500 mg twice a day for seizure prophylaxis. After 3rd dose, the patient developed diffuse, erythematous and itchy rashes over whole body without any breathing difculties. Levetiracetam was discontinued, and tablet lacosamide 200 mg twice daily was substituted. After 1 day, the rash dissipated. Our case was classied as drug-induced urticaria with red itchy hives. The world health organization Uppsala monitoring Centre (WHO-UMC) causality assessment system suggested a probable/likely cause for levetiracetam-induced skin reaction. Levetiracetam seemingly have fewer side effects than the traditional antiepileptic medications but it is important for the healthcare providers to continuously monitor the medication for adverse effects, so that necessary modications and required labeling may be reformed in-time.

Direct reporting of adverse drug reactions by healthcare consumers in Africa: a narrative review.

Background The challenges of under-reporting of adverse drug reactions have been identified as a major setback for the pharmacovigilance system worldwide. Direct reporting by health care consumers has been adopted in some developed and developing countries with a positive impact in improving pharmacovigilance activities through increased reporting rate. There are limited reports on direct reporting and its outcome in Africa. Aim of the review The study aimed to identify and present the available evidence on direct reporting of adverse drug reactions by healthcare consumers in Africa. Methods A review guided by Cochrane handbook was conducted. Electronic scientific databases such as PubMed, Cumulative Index to Nursing and Allied Health Literature, Embase and Cochrane Library were searched. Google scholar, general Google search engine, the website for the regulatory resources for Africa and World Health Organisation-Uppsala Monitoring were also searched for available guidelines, documents and publications. The review period was January 1992 to October 2019. The results were analysed descriptively. Results This study identified 16 African countries that have included healthcare consumers as eligible to report adverse drug reactions in their policy/guidelines. There is low awareness of healthcare consumers on pharmacovigilance system. Eight (8) out of thirty-six (36) African countries that are members of the World Health Organisation Programme for International Drug Monitoring have formally launched direct reporting by healthcare consumers which are 14.2% of African countries. There is a wide range of difference between the rate of adverse drug reactions report submitted by health care consumers as compared with healthcare workers. Paper form, text messages, telephone and web application-based reporting system have been used by different countries that have launched direct reporting. Poor infrastructure, low awareness and lack of a reporting culture are major challenges while the availability of common reporting methods is a potential opportunity of promoting direct reporting in African countries. Conclusions Few African countries have adopted and launched direct reporting. Reporting rate through direct methods is still relatively low when compared with reporting by healthcare workers. Published legal framework, policies, guidelines and studies on direct reporting are limited. Availability of a system and reporting method are opportunities to improve and overcome probable challenges.

A comparative study of active and passive adverse drug reaction reporting systems in terms of false reporting rate

Background: World Health Organisation Uppsala Monitoring Centre (WHO-UMC) was set up in 1968 to collect Adverse Drug Reactions (ADRs) periodically for all drugs across the globe. It identifies two main approaches to pharmacovigilance: active (intensive) and passive (spontaneous). However, very few studies are available to compare these two methods of adverse drug reaction reporting. Methods: A prospective observational study was done on 303 newly diagnosed patients with tuberculosis receiving directly observed therapy short-course (DOTS) in the Sawai Man Singh (SMS) Hospital, Jaipur between 1 January 2019 and 31 December 2019. They were randomly divided into groups A (150 patients) and B (153 patients). Group A patients were followed actively at fixed intervals of time for ADRs till next six months through electronic conversation or personal interview. Group B patients were required to report spontaneously for any ADRs to pharmacovigilance centre. After data collection causality assessment was done using the WHO-UMC scale to identify false reporting and finally results were analysed statistically by means of the t-test using Minitab 14 software Pennsylvania, USA. Results: 153 ADRs were reported in active and 39 in passive group. Hence the yield of ADR was four times more in active method. After causality assessment, 31 in group A and 12 in group B were found to be falsely related (unlikely) to antitubercular drugs. Two sample t-test revealed active method reported more false ADR (p = 0.005). Conclusion: Although active method of surveillance identifies more ADRs than passive method, it is also more prone to false reporting. Hence its benefits should be weighed against its cost before adopting it for countries with limited resources.

Shivering Due to Repeat Dose of Tranexamic Acid: A Peculiar Case Series

Tranexamic acid (TXA) is a well-tolerated hemostatic agent that has been in clinical use for nearly 60 years. In this report, we describe for the first time 10 patients who experienced adverse reactions to repeat dose of TXA, which were not seen with the first dose. Shivering was found to be the most common adverse reaction. In half of the cases, shivering was associated with low-grade fever. On dechallenge and subsequent administration of steroids and antihistaminic agents, the reactions were controlled. On assessment with the World Health Organization–Uppsala Monitoring Centre scale, the causality was ascertained to be “Probable”.There is no clear postulated mechanism for shivering with TXA. We have postulated that hypersensitivity, fever, and shivering in these patients may be interlinked. In the light of this report, the physicians should take into account that repeated challenge with TXA may lead to adverse reactions in some patients and withdrawing the drug in such patients may be required.

Natural Health Product-Drug Interaction Causality Assessment in Pediatric Adverse Event Reports Associated with Attention-Deficit/Hyperactivity Disorder Medication.

Background: Some pediatric patients with attention-deficit/hyperactivity disorder (ADHD) use natural health products (NHPs) such as herbal remedies. Although herbal remedies are generally considered to be safe when they are used appropriately, they may contain active components that can interact with medications being used concurrently, with potential for NHP-drug interactions leading to adverse events. Objectives: The objectives of this study were (1) to identify adverse event reports (AERs) involving commonly used herbal remedies and ADHD prescription medicines in children and adolescents; (2) to evaluate the quality of collected AERs; and (3) to assess whether NHP-drug interactions can be causally linked to reported adverse events. Methods: We systematically searched the FDAble database (FDAble.com) for herbal remedies commonly used by patients (4-18 years old) also taking ADHD drugs from 1997 to 2015. We assessed the completeness of the AERs and used three causality assessment tools modified for NHPs (Naranjo Adverse Drug Reaction Probability Scale, HORN Drug Interaction Probability Scale, and World Health Organization Uppsala Monitoring Centre Scale). Results: Of the 23 identified AERs involving both an herbal remedy and an ADHD prescription medication, most involved multiple (>3) substances with inadequate detail to assess multiple potential interactions. Following data extraction and evaluation of completeness, five AERs involving only one herbal remedy and one ADHD medication were evaluated for causality. An NHP-drug interaction was assessed to be probable in one case and to be possible in another. Both these reports involved a methylphenidate formulation and St. John's wort. Conclusions: Eighteen of the 23 identified AERs involving both an herbal remedy and an ADHD drug also involved other multiple ingredient products. The reporting quality was poor for the five AERs examined. Further research is needed to study the interaction between St. John's wort and methylphenidate.

91 A Descriptive Analysis of Causative Drgs/Drg Classes of Incident Adverse Drg Reactions in Acutely Hospitalized Older-Adults: SENATOR (Phase I)

Abstract Background Adverse drug reactions (ADRs) are common and have serious repercussions for older-adults. This descriptive-analysis elucidates clinical presentations, severity and responsible drugs of incident ADRs in the SENATOR (Software ENgine for the Assessment & optimization of drug and non-drug Therapy in Older peRsons) phase I feasibility study. Methods SENATOR-phase-I was a European multicentre-prospective-observational study. Participants were ≥ 65 years, experiencing acute-hospitalisation and on pharmacological treatment for ≥ 3 conditions. Adverse events (AEs) were identified by trigger list at recruitment, day-14/discharge and classified as ADRs when association with an administered drug was adjudicated as being probable/certain, according to the World Health Organization Uppsala Monitoring Centre ADR causality criteria. Results Of 644 participants recruited, 382 (59.1%) experienced 732 AEs, 363 AEs (49.6%) being incident. 139 participants (21.6%) experienced 177 (48.8%) ADRs. Full drug details were recorded in 156 patients (88%). Cardiovascular-system drugs accounted for one-third of ADRs (55, 35.3%). Five drug classes caused three-quarters of ADRs (135, 76.3%); diuretics 28.2% (furosemide 24.4%), opioid analgesics 16.7%, anti-bacterials for systemic use 14.1%, anti-thrombotic agents 10.3%, and drugs used in diabetes 7%. 68 patients (10.6%) experienced 81 (45.8%) clinically significant moderate-severe ADRs. Significant serum electrolyte disturbance (32, 18.1%), acute kidney injury [AKI] (22, 12.4%), unspecified adverse event (UAE; 21, 11.9%), dyspepsia/nausea/vomiting (20, 11.3%), new-onset major constipation (19, 10.7%) were the most common presentations of ADRs, accounting for 114, (64.4%) of all ADRs. In moderate-severe ADRs; AKI (12, 14.8%), acute bleeding (11, 13.6%), new-onset major constipation (11, 13.6%), UAE (11, 13.6%), significant serum electrolyte disturbance (10, 12.4%) were the most common presentations. Conclusion This analysis highlights that; 1-in-5 older adults will experience an incident ADR during acute hospitalisation. 1-in-10 patients experience moderate-severe incident ADRs. 3-of-4 ADRs were caused by 5 drug classes (diuretics, opioids, anti-bacterials, anti-thrombotics and anti-diabetic agents). This study allows for identification of potentially high risk medications which could be targeted for future ADR prevention.