World Health Organization Causality Assessment Research Articles

Chronic Immune Thrombocytopenia Purpura Following COVID-19 Vaccination (ChAdOx1 –nCov-19): A Case Report With OneYear Follow-Up

Background: Immune Thrombocytopenia Purpura (ITP) is a hematological disorder, where its primary cause is unknown. This can be triggered through any secondary underlying diseases or other environmental agents such as drugs, vaccination, natural viral infections etc. After the introduction of COVID-19 vaccines, a 4-fold increase in ITP cases was observed globally. Many of the COVID-19 vaccines such as m-RNA and viral-vector vaccines already demonstrated a cause-effect relationship between the event of ITP and immunization. Case presentation: A 54 year old diabetic patient presented to the hospital with complaints of gum bleeding and fatigue. He was diagnosed with severe ITP following COVID-19 vaccination with a platelet count of 5000 cumm. Initially his condition was considered as idiopathic and the COVID-19 vaccine exposure (13 days prior to the clinical presentation) was not suspected. Later the immunization timeline and onset of the reaction was traced by his hematologist. The patient underwent multiple platelet transfusions and was given corticosteroid therapy. The patient was followed for a period of 1 year and throughout the follow-up period the patient had fluctuating platelets count, especially after tapering steroids. Conclusion: ITP in this case is found to have a consistent causal association to COVID-19 vaccination as per the World Health Organization Causality assessment algorithm and is categorized under vaccine product related reactions. One year follow-up conducted showed that the thrombocytopenia following COVID-19 vaccine may be prolonged.

Adverse drug reactions of oral non-steroidal anti-inflammatory drugs and its fixed drug combinations: A 5-year retrospective observational study

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are very commonly prescribed worldwide. Due to this, the incidence of adverse drug reactions (ADRs) to NSAIDs is increased. Aims and Objectives: This study aims to analyze the ADRs reported to NSAIDs. Patient demographics, organ system affected severity of ADRs, and their causal association with the drug will be studied. Materials and Methods: It was a retrospective analysis of ADRs reported to oral NSAIDs and its combinations over a period of 5 years from January 2015 to December 2020. Prior ethics committee approval was obtained. These ADRs were collected as part of pharmacovigilance activities. Results: A total of 100 ADRs were reported due to NSAIDs. Most ADRs due to NSAIDs were reported in 30–39 years age group. Female gender was most affected by ADRs. Diclofenac was the most common NSAID causing ADRs. Skin and subcutaneous organ system was most affected. Six ADRs were reported as serious. Sixty-seven ADRs were categorized as probable using the World Health Organization causality assessment scale. Conclusion: NSAIDs are commonly prescribed drugs. Analyzing the ADRs reported to NSAIDs will help in finding the risk factors. Based on this knowledge, rational prescription of NSAIDs can be done which will improve the patient safety.

Ocular Adverse Events after Inactivated COVID-19 Vaccination in Xiamen.

Aims: To report potential vaccine-induced ocular adverse events following inactivated COVID-19 vaccination (Sinopharm and Sinovac). Methods: This case series took place at a tertiary referral center in the southeast of China (Xiamen Eye Center in Fujian Province) from February 2021 to July 2021. Patients who received the first dose of inactivated COVID-19 vaccine and developed vaccine-related ocular adverse events within 10 days were included. The diagnosis of vaccine-related ocular adverse events was guided by the World Health Organization causality assessment and the Naranjo criteria. Results: Ten eyes of seven patients (two male individuals) presenting with ocular complaints following COVID-19 vaccine were included in the study. The mean (SD) age was 41.4 (9.3) years (range, 30–55 years). The mean time of ocular adverse event manifestations was 4.9 days (range, 1–10 days). Three patients were diagnosed with Vogt–Koyanagi–Harada (VKH)-like uveitis, one with multifocal choroiditis, one with episcleritis, one with iritis, and one with acute idiopathic maculopathy. Two patients received the second dose of vaccine. One patient had exacerbation of VKH, and one patient had no symptoms. An aqueous humor analysis in three patients revealed elevated proinflammatory cytokines and negative virus copy. All the patients had transient ocular disturbance and responded well to steroids. No recurrence was noted during 6 months of follow-up. Conclusions: Potential ocular adverse events should be reported to increase the awareness of the health community for timely detection and proper treatment.

Evaluation of voriconazole related adverse events in pediatric patients with hematological malignancies.

Despite therapeutic drug monitoring and pharmacogenetic-guided dose selection are recommended for pediatric patients, safety of voriconazole is mostly monitored by clinical assessment. Having comprehensive knowledge of safety profile and distinguishing incidental events from the reactions that are truly related to voriconazole use are crucial for safer and uninterrupted treatment. This study aimed to address adverse reactions during the first month of voriconazole use by systematically evaluating retrospective records of all adverse events. Patients/Methods: It is a single-center, retrospective analysis of patients who received voriconazole from 1 September 2010 to 1 September 2020. Severity of abnormal findings in medical records were systematically graded. Causality between voriconazole and the events was evaluated by Liverpool Causality Assessment Tool (LCAT), Naranjo Algorithm and World Health Organization Causality Assessment System. The events with possible or probable causal relation to voriconazole are classified as adverse reaction. Records of 45 patients included in the study. The overall frequency of adverse reactions was 51.1%. Hepatobiliary laboratory adverse reactions identified in 48.9% of the patients and led to treatment discontinuation in 20.0%. Amylase and lipase elevation (2.2%), ventricular extra systoles (2.2%), hallucination and nightmares (2.2%) were other adverse reactions. Hepatobiliary abnormalities were the most common adverse reactions and the most common cause of treatment discontinuation. For safer treatment in critically ill patients, the dose should be personalized. To clearly identify the accurate frequency and the causality of all adverse reactions, prospective studies with much larger sample size are needed.

Post-Marketing Active Surveillance of Adverse Reactions Following Influenza Cell-Based Quadrivalent Vaccine: An Italian Prospective Observational Study.

Since the influenza season 2018/19, the Italian Ministry of Health recommended a dose of cell-based quadrivalent vaccine (Flucelvax Tetra) for HCWs (healthcare workers), because this vaccine seemed more efficacious in the prevention of AH3N2 virus. Due to the lack of pre-registration data, the safety profile of this new vaccine must be investigated in post-marketing surveillance. The aim of our study is to evaluate, through a post-marketing active surveillance program developed during the 2019/20 influenza season, any Adverse Events Following Immunization (AEFIs) that happened in the 7 days after immunization with Flucelvax Tetra. The study was carried out in a sample of HCWs of Policlinico General University-Hospital (Apulia, South Italy). AEFIs were classified as ‘serious’ or ‘not serious’ according to the WHO (World Health Organization) guidelines; the WHO causality assessment algorithm was applied to classify serious AEFIs. A total of 741 HCWs were enrolled, and 430 AEFIs (reporting rate: 58.0 (95%CI: 54.4–61.6) × 100 enrolled) were recorded. Of these, 429 of 430 (99.8%; reporting rate: 57.8 (95%CI: 54.2–61.5) × 100 enrolled) were classified as not serious and one (0.2%; reporting rate: 0.13 (0.03–0.75) × 100 enrolled) was classified as serious. Local reactions were the adverse reaction reported most frequently (88%); regarding the serious AEFI, causality assessment excluded the causal link with the administration of the vaccine. All the AEFIs resolved without sequelae. Flucelvax Tetra showed a profile of high safety. Due to their characteristics of greater sensitivity than passive surveillance, active surveillance programs can be useful in defining the safety profiles of a given vaccine/drug in certain population subgroups.

Adverse events following pediatric immunization in an Indian city.

PurposeAdverse effects are noticeable immediately after vaccination, especially when vaccinated to healthy people at the time of vaccination. The vaccine may cause adverse events which are very rare but adverse event following immunization surveillance becomes correspondingly more important in a less studied population like India. Hence, there is a need for carrying out a study pertaining to vaccine safety in the pediatric population of age 0–12 years and assessing the events occurring post-vaccination.Materials and MethodsA prospective observational study was conducted in three primary healthcare centers and two tertiary care hospitals for 6 months from April 2016 to September 2016 with a total of 826 children enrolled. Detected adverse events for suspected vaccines were analyzed for causality by the World Health Organization causality assessment instrument. Sex-specific differences in incidences of adverse events were assessed.ResultsThe cumulative adverse events were found highest in pentavalent vaccines (510 incidences, 62.04%) followed by the bacillus Calmette-Guérin vaccine (189 incidences, 22.99%). The study didn’t reveal any significant association in incidences of adverse events following immunization and sex of the children.ConclusionVaccine safety surveillance studies are need of the hour in developing countries to maintain public trust in vaccines, the ultimate objective being to have vaccines with the most favorable benefit-risk profile. The present study discussed the various adverse events following immunization and suggested the absence of any sex-specific difference in incidences of adverse events in children.

Eltrombopag for Immune Thrombocytopenia in Adult Patients in the Real-World in France. Final Results of the Elextra Study

Introduction:Eltrombopag has been available in Europe for the treatment of chronic primary immune thrombocytopenia (ITP) since 2010. Since 2019, it has been indicated in patients with primary ITP, lasting 6 months or longer from diagnosis and who are refractory to other treatments, aged 1 year and above. However, data are lacking regarding the use, the efficacy and the safety of eltrombopag in clinical practice in Europe. The ELEXTRA study aimed to assess these questions in France. The intermediate results were presented at the 2019 ASH Annual Meeting. We present here the final results of the ELEXTRA study. Methods:Population source was the CARMEN-France registry. The CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry is aimed at the prospective follow-up of all incident ITP adults in the French Midi-Pyrénées region (South-West of France, 3 million inhabitants) since June 2013. Each investigator follows all adult patients (aged ≥18 years) newly diagnosed with ITP in routine visits or hospital stays, and detailed information on patients' characteristics and management of ITP are prospectively recorded. This registry has been implemented in other French centers since 2016, taking the name of CARMEN-France. ITP was defined by platelet count <100 x 109/L and exclusion of other causes of thrombocytopenia. The study population consisted of all incident ITP adults included in the CARMEN-France registry from June 2013 to December 2019 who were exposed to eltrombopag during the disease course. We described the time from ITP diagnosis to first exposure to eltrombopag, and patients' characteristics. Efficacy was assessed in patients who had a platelet count <30 x 109/L at eltrombopag initiation. Overall response was defined by platelet count ≥30 x 109/L and complete response by platelet count ≥100 x 109/L. Adverse drug reactions (ADRs) that occurred during eltrombopag exposure were collected and assessed according to the World Health Organization causality assessment scale. All ADRs with causality score assessed at least as "possible"were described. Results:Out of 795 patients included in the registry, 156 (19.6%) had been exposed to eltrombopag for a median duration of 100 days (range: 1-1427). Mean age was 60.2 years (standard deviation: 20.9) and 79 (50.6%) were males; 60 (38.5%) had at least one comorbidity of the Charlson Comorbidity Index score; 89 (57.1%) had at least one cardiovascular risk factor (not including age and sex) and 9 (5.8%) a history of venous thrombosis. At ITP diagnosis, the median platelet count was 8 x 109/L (range: 1-88 x 109/L) and 118 (75.6%) patients had bleeding. Median time from ITP onset to first exposure to eltrombopag was 3.3 months (range: 0.1-82.2): 74 (47.4%) patients were exposed before 3 months of ITP duration, 21 (13.5%) between 3 and 6 months and 61 (39.1%) after 6 months. Exposures to ITP treatments before eltrombopag initiation were: corticosteroids in 150 (96.2%) patients, intravenous immunoglobulin (IVIg) in 106 (67.9%), dapsone in 28 (17.9%), rituximab in 26 (16.7%), romiplostim in 12 (7.7%), hydroxychloroquine in 14 (9.0%), danazol in 8 (5.1%), vinblastine in 5 (3.2%), azathioprine in 2 (1.3%), ciclosporin in 1 (0.6%) and splenectomy in none. Eltrombopag was used as second-line agent in 52 (33.3%) patients and third-line in 56 (35.9%). Among the 156 patients, 75 (48.1%) had a platelet count <30 x 109/L at eltrombopag initiation; among them, 65 (86.7%) achieved overall response and 53 (70.7%) complete response at any time during exposure to eltrombopag. Among the 65 patients who achieved overall response, 58 (89.2%) had a concomitant exposure to another ITP treatment at eltrombopag initiation (including steroids, n=42; IVIg during the past month, n=44; rituximab in the past 6 months, n=11). Overall, 47 ADRs were reported: the most frequent were: thrombocytosis (n=10), thrombosis (n=8: 6 pulmonary embolism, 1 deep and 1 superficial vein thrombosis), rash (n=4), hepatitis (n=3),and headache (n=3). Conclusion:In French real-world practice, eltrombopag is used early in the ITP course. Efficacy is similar to that observed in clinical trials. The safety profile identified in clinical trials is also confirmed. Disclosures Moulis: Grifols: Research Funding; Amgen: Other: meeting attendance grant; Novartis SAS: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance grant, Research Funding. OffLabel Disclosure: Real-World use of eltrombopag in immune thrombocytopenia

Eltrombopag for Immune Thrombocytopenia Adult Patients in the Real-Life Practice in France. Interim Results of the Elextra Study

Eltrombopag for Immune Thrombocytopenia Adult Patients in the Real-Life Practice in France. Interim Results of the Elextra Study

Study of adverse drug reactions to antiretroviral therapy in a tertiary care hospital, Tirupati.

Purpose:Human immunodeficiency virus-infected patients do not adhere to their antiretroviral therapy (ART) due to adverse effects of drugs. The continuous monitoring of adverse drug reactions (ADRs) may ensure the safe use of drugs in patients. Hence, a retrospective analysis was carried out to assess the ADRs pattern, causality, and severity associated with various antiretroviral drug regimens in patients receiving ART.Materials and Methods:A retrospective, analytical study was carried out at ART nodal center in Sri Venkateswara Ramnarain Ruia Government General Hospital, Tirupati. Data were collected by spontaneous reporting of health-care professionals from ART centers using Suspected ADR Reporting Forms of Indian Pharmacopoeia Commission to record the ADRs occurred in the patients who underwent treatment from December 2015 to November 2016. A total of 299 ADR reports were collected during the study period. The causality and severity of the reported ADRs were assessed using suitable scales.Results:From a total of 299 ADR reports, females (63.81%) experienced higher ADRs than males (36.12%). The highest number of ADRs was reported to zidovudine/lamivudine/nevirapine (ZLN) regimen (76.92%) than tenofovir/lamivudine/efavirenz (TLE) regimen (23.07%). Cutaneous reactions were higher (34.34%) among patients receiving ZLN therapy, and drowsiness (53.62%) was the most common ADR in patients receiving TLE regimen. According to the World Health Organization causality assessment scale, most of the ADRs were possible (75.92%). On the assessment of Modified Hartwig and Siegel Severity Scale, 55.09% of ADRs were moderate.Conclusion:The study showed an increased incidence of ADRs to ART which calls for efficient pharmacovigilance systems to improve patient care and drug safety.

Systematic causality assessment of adverse events following HPV vaccines: Analysis of current data from Apulia region (Italy)

Since 2013, World Health Organization (WHO) recommended that adverse events following immunization (AEFIs) should be evaluated by a standardized algorithm for causality assessment, however the use of WHO procedure is rarely adopted. In Italy, AEFIs (classified only by temporal criteria) are registered in the National Drug Authority (AIFA) database, but causality assessment is not mandatory. Every year AIFA publishes the AEFIs report, that doesn’t contain information about causal correlation between events and vaccines. From AIFA database, we selected AEFIs following human papillomavirus vaccination (HPV) reported in Apulia (about 4,000,000 inhabitants) during 2008–2016. For serious AEFIs, we applied WHO causality assessment criteria; for cases hospitalized, we repeated the assessment getting additional information from health documentation. In 2008–2016, 100 HPV AEFIs (reporting rate: 17.8 per 100,000 doses) were registered of which 19 were serious (rate: 3.4 per 100,000 doses) and 12 led to hospitalization. After causality assessment, for 9 AEFIs the classification was “consistent causal association to immunization”, for 3 indeterminate, for 5 “inconsistent causal association to immunization” and for 2 not-classifiable. Among hospitalized patients, 5 AEFIs were consistent, 5 inconsistent, 1 not-classifiable and 1 indeterminate; adding information from health documentation, the results were similar except for indeterminate and not classifiable AEFIs that turned into “not consistent”. Only half of severe AEFIs could be associated with vaccination and this suggests that AIFA report provides a incomplete picture of HPV vaccine safety, with a risk for readers to confound “post hoc” and “propter hoc” approach without considering the causality assessment results. In the view of the systematic use of WHO causality assessment algorithm in the AEFI surveillance, the efforts of Public Health must be focused on the improvement of the quality of the information provided to reduce conclusions inter-observer variability; the routine follow-up of reports, also to collect additional information, must be guaranteed.

Application of the revised WHO causality assessment protocol for adverse events following immunization in India

BackgroundIn 2013, the World Health Organization (WHO) and CIOMS introduced a revised Causality Assessment Protocol (CAP) for Adverse Events following Immunization (AEFI). India is one of the first countries to adopt the revised CAP. This study describes the application of the revised CAP in India. MethodsWe describe use of CAP by India’s AEFI surveillance program to assess reported AEFIs. Using publicly available results of causality assessment for reported AEFIs, we describe the results by demographic characteristics and review the trends for the results of the causality assessment. ResultsA total of 771 reports of AEFI between January 2012 and January 2015, completed causality review by August 2016. The cases were reported as belonging to a cluster (54%; n=302), hospitalized or requiring hospitalization (41%; n=270), death (25%; n=195), or resulting in disability (0.4%; n=3). The most common combinations of vaccines leading to report of an AEFI were DTwP, Hepatitis B, and OPV (14%; n=106), followed by Pentavalent and OPV (13%; n=103), and JE vaccine (13%; n=101). Using the WHO Algorithm, most AEFI reports (89%, n=683) were classifiable. Classifiable AEFI reports included those with a consistent causal association (53%; n=407), an inconsistent causal association (29%; n=226) or were indeterminate causal association with implicated vaccine(s) or vaccination process (6.5%; n=50) (Fig. 1); 88 reports remained unclassifiable. ConclusionsThe revised CAP was informative and useful in classifying most of the reviewed AEFIs in India. Unclassifiable reports could be minimized with more complete information from health records. Improvements in causality assessment, and standardization in reporting between countries, can improve public confidence in vaccine system performance and identify important vaccine safety signals.

Incidence and risk estimate of drug‐induced agranulocytosis in Hong Kong Chinese. A population‐based case–control study

Drug-induced agranulocytosis is a rare but life-threatening adverse drug reaction. Its epidemiology in Chinese is largely unknown. This study aimed to estimate the incidence, mortality, and risk of the drugs associated with agranulocytosis in Hong Kong Chinese. A population-based case-control study was conducted using the Clinical Data Analysis and Reporting System, a database managed by the Hong Kong Hospital Authority. Patients with drug-induced agranulocytosis from 1 January 2004 to 31 December 2013 were identified. World Health Organization causality assessment was used to evaluate the possible drug aetiology of each case. Odd ratios (ORs) of the drug exposure were calculated using exact conditional logistic regression. A total of 155 cases of drug-induced agranulocytosis were identified. Mean age was 51.4 years, and 95 cases were female. Incidence rate was estimated to be 2.2 cases per million person-years, and the all-cause mortality of patients with drug-induced agranulocytosis was 3.9%. Among the cases, the most common associated drug groups were antithyroid drugs (41.9%), antimicrobials (20%), anticonvulsants (10.3%), and antipsychotics (6.5%). Carbimazole had the highest risk of agranulocytosis (adjusted OR 416.7, 95% confidence interval (CI) 51.5-3372.9) with an incidence of 9.2 (95%CI 6.9-12.1) per 10 000 users and 3.6 (95%CI 2.7-4.8) per 10 000 user-years. Other drugs with significant risk included cephalosporins, clozapine, penicillins, phenytoin, and propyl thiouracil. The incidence and mortality in Hong Kong Chinese were relatively low compared to Caucasians. Antithyroid drugs were the most common implicated drug class, and carbimazole had the highest risk of agranulocytosis. Copyright © 2017 John Wiley & Sons, Ltd.

Pharmacovigilance Study on Platinum-based Chemotherapeutic Regimens in Oral Cancer Patients: A Prospective Cohort Study

Platinum-based chemotherapy is one of the most common therapies employed in oral cancer treat-ment. This is a prospective cohort study to analyse the pattern and incidence of adverse drug reac-tions to platinum based chemotherapeutic regimens in oral cancer patients. Pharmacovigilance studies are still unexplored in oral cancer patients in Bihar (India). Oral cancer patients who received platinum-based cancer chemotherapy were monitored for adverse drug reactions. The collected re-ports analysed for demographic, causality, preventability and severity of adverse drug reactions. Causality was assessed by the World Health Organization causality assessment scale. Preventability and severity of adverse drug reactions assessed by modified Schumock and Thornton scale, modified Hartwig and Siegel scale respectively. Incidence rate, relative risk and attributable risk were evaluat-ed among the regimens. Out of 120 patients, 108 (90%) patients were males. 105 patients (87.5%) developed a total of 247 adverse drug reactions. World Health Organization UMC causality scale showed 82% of adverse drug reactions were “certain”, 15% were “probable” and 3% were “possi-ble”. Modified Hartwig and Siegel severity scale showed 89% of adverse drug reactions were “mild” and 11% were “moderate” type. Schumock and Thornton preventability scale showed 93% of ad-verse drug reactions were “not preventable” and 20% were “probably preventable”. Paclitax-el+carboplatin regimen showed lowest values in terms of adverse drug reactions. Platinum-based chemotherapy was used in the treatment of oral cancer. From this study it is evident that paclitax-el+carboplatin regimen reported least incidence rate of adverse drug reactions among platinum regi-mens. Incidence rate was more reported in cisplatin regimen.

Pattern of adverse drug reactions due to cancer chemotherapy in a tertiary care hospital in South India.

Purpose:Studies regarding pattern of adverse drug reactions (ADRs) in cancer chemotherapy patients are scarce in India. This study was conducted to evaluate the pattern of occurrence of ADRs due to cancer chemotherapy in hospitalized patients and to assess the causality, severity, predictability, and preventability of these reactions.Materials and Methods:This was a retrospective, descriptive study and the occurrence and nature of ADR, suspected drug, duration of hospital stay and outcome were noted from case records. These ADRs were assessed for causality using both World Health Organization (WHO) causality assessment scale and Naranjo's algorithm. The severity and preventability of the reported reactions were assessed using modified Hartwig and Siegel scale and modified Schumock and Thornton scale respectively.Results:Five hundred ADRs were recorded from 195 patients. Most common ADRs were infections (22.4%), nausea/vomiting (21.6%) and febrile neutropenia (13%). Platinum compounds, nitrogen mustards, taxanes, antibiotics and 5-fluorouracil were the most common drugs causing ADRs. WHO causality assessment scale showed 65% of the reactions to be “probable” and 35% to be “possible”, while Naranjo's algorithm indicated that 65.6% of ADRs were “probable” and 34.4% were “possible”. Modified Hartwig and Siegel scale showed most reactions (41.4%) to be of “moderate level 4(a)” severity, while 30.6% of reactions were of “mild level 1” severity. About 30.8% of the ADRs were “definitely preventable” according to the modified Schumock and Thornton scale.Conclusion:ADRs are most important causes of morbidity and mortality and increase the economic burden on patient and society. By careful ADR monitoring, their incidence can be decreased.

Adverse drug reaction profiles of commonly used platinum compounds in cancer chemotherapy

Background: The aim of the present study was to monitor and analyze the pattern of occurrence of adverse drug reactions (ADRs) to commonly used platinum compounds in MNJ Cancer Hospital, Hyderabad. Methods: Cancer patients, who received platinum compounds as chemotherapy regimen, were monitored for adverse reactions. Cancer patients belonging to either gender and of all ages, who were receiving platinum compounds under any standard regimen, were included for the study. Cases that were unlikely, conditional or unaccessible under World Health Organization (WHO)-Uppsala Monitoring Centre causality criteria were excluded from the study. The ADRs were recorded in Central Drugs Standard Control Organization forms. Causality was assessed by the WHO Causality Assessment Scale and Naranjo’s Algorithm. Preventability and severity of ADRs were assessed by modified Schumock and Thornton scale, modified Hartwig and Siegel scale, respectively. Results: Among 100 patients, 78 developed ADRs to platinum compounds. The reactions observed were vomiting, diarrhea, abnormal renal function tests, myelosuppression, anemia, thrombocytopenia, alopecia, and constipation. The WHO Causality Assessment Scale indicated 64.6% “possible” and 35.4% “probably,” but no “certain” reactions. Naranjo’s Algorithm showed 59.4% “possible” 40.6% “probable” reactions. 48% reactions were “definitely preventable” 16% were “probably preventable” and 36% were “not preventable.” Modified Hartwig and Siegel Scale of severity assessment showed that 12% reactions were “mild” 69% were “moderate” and 19% were severe. Conclusion: Platinum compounds have high potential for adverse effects. There is a need to improve the management of adverse effects. This study also emphasizes the need to improve pharmacovigilance awareness among physicians in order to improve the pharmacovigilance in India.

Prospective Observational Study of Adverse Drug Reactions of Anticancer Drugs Used in Cancer Treatment in a Tertiary Care Hospital.

Adverse drug reactions associated with the use of anticancer drugs are a worldwide problem and cannot be ignored. Adverse drug reactions can range from nausea, vomiting or any other mild reaction to severe myelosuppression. The study was planned to observe the suspected adverse drug reactions of cancer chemotherapy in patients aged >18 years having cancer attending Postgraduate Institute of Medical Education and Research, Chandigarh. During the study period, 101 patients of breast cancer and 73 patients of lung cancer were screened for occurrence of adverse drug reactions during their treatment with chemotherapy. About 87.36% patients experienced adverse drug reactions, 90.09% and 83.56% of breast and lung cancer patients experienced at least one adverse drug reaction respectively. In breast cancer patients, 41.58% patients were prescribed fluorouracil+doxorubicin+cyclophosphamide while paclitaxel was prescribed to 22.77% patients. Alopecia (54.94%), nail discolouration (43.96%), dysgeusia (38.46%), anorexia (30.77%), nausea (29.67%), and neuropathy (29.67%) were found to be very common in breast cancer patients treated with single/combined regimen. In lung cancer group of patients, cisplatin with docetaxel, cisplatin with pemetrexed and cisplatin with irinotecan were prescribed to 30.14, 24.65 and 17.81% patients, respectively. Dysgeusia (40.98%), diarrhoea (39.34%), anorexia (32.77%) and constipation (31.15%) and alopecia (31.15%) were commonly observed adverse drug reactions having lung cancer patients. Causality assessments using World Health Organization causality assessment scale showed that observed adverse drug reactions were of probable (64.67%) and possible (35.33%) categories. Alopecia, dysgeusia, anorexia, constipation diarrhoea, nausea, nail discoloration were more prevalent amongst the cancer patients undergoing chemotherapy.

Drug utilization pattern of antiseizure drugs and their adverse effects in the pediatric population, in a tertiary care hospital attached to a medical college

Background: Epilepsy is “a condition characterized by recurrent (two or more) seizure, unprovoked by any immediate identified cause.” The desired outcome of antiseizure drug (ASD) therapy is to be seizure-free throughout the rest of life. The objective was to study the utilization pattern and adverse drug reactions (ADRs) associated with the use of ASDs in pediatric outpatients in epilepsy clinic. Methods: This cross-sectional, observational and single center study was carried out over a period of 1 year in 430 pediatric patients. Analyzed data included demographic details and drugs prescribed in respective seizure types along with ADRs due to ASDs. Results: In a total 430 patients analyzed, seizure were most commonly observed in boys (69.8%) in 6-10 year of age (45.3%), with a positive family history in (16%), with no specific cause of seizure in (71.6%), with most common type was focal seizure in (62.3%), which was mainly treated with carbamazepine (73.8%). Most common ADR was irritability (32.2%) with Valproate being main drug. 87.3% ADRs were in “ possible” as per World Health Organization causality assessment scale, 94.9% ADRs were “mild” as per Hartwig and Siegel severity assessment scale and 98.3% ADRs were “preventable” as per Schumock and Thornton preventability scale. Conclusion: Focal seizure was most common type of seizure observed mainly in boys of 6-10 year with carbamazepine as mainly prescribed drug. Use of appropriate ASDs in the majority of patients as per guidelines, has decreased number of ADRs in our study. Prescribing drugs were mainly from essential drug list and by generic names.

Gastrointestinal Adverse Events with Sodium Polystyrene Sulfonate (Kayexalate) Use: A Systematic Review

BackgroundSodium polystyrene sulfonate (Kayexalate; Sanofi-Aventis, Paris, France) is a cation-exchange resin routinely used in the management of hyperkalemia. However, its use has been associated with colonic necrosis and other fatal gastrointestinal adverse events. Although the addition of sorbitol to sodium polystyrene sulfonate preparations was previously believed to be the cause of gastrointestinal injury, recent reports have suggested that sodium polystyrene sulfonate itself may be toxic. Our objective was to systematically review case reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use. MethodsMEDLINE (1948 to July 2011), EMBASE (1980 to July 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (1993 to July 27, 2011), bibliographies of identified articles, and websites of relevant drug agencies and professional associations in the United States and Canada were reviewed to identify eligible reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use. Causality criteria of the World Health Organization causality assessment system were applied to each report. ResultsThirty reports describing 58 cases (41 preparations containing sorbitol and 17 preparations without sorbitol) of adverse events were identified. The colon was the most common site of injury (n=44; 76%), and transmural necrosis (n=36; 62%) was the most common histopathologic lesion reported. Mortality was reported in 33% of these cases due to gastrointestinal injury. ConclusionsSodium polystyrene sulfonate use, both with and without sorbitol, may be associated with fatal gastrointestinal injury. Physicians must be cognizant of the risk of these adverse events when prescribing this therapy for the management of hyperkalemia.

A prospective study of adverse drug reactions to artemisinin-based combination therapy in a tertiary care hospital in India

Objectives:Antimalarial drugs are commonly prescribed for the treatment of malaria and suspected cases of malaria in India. The recent trend is to prescribe ACT and the incidence of adverse reactions to this therapy is notwell-documented in Indian population. Therefore, this study was designed to assess ADR pattern of antimalarial drugs particularly ACT in India.Materials and Methods:Over a period of 1 year, 500 patients who were administered antimalarial drugs were enrolled in the study. The World Health Organization causality assessment scale was used for classifying the ADR.Results:In this study out of 500 patients, 251 complained of ADRs. The sex-wise difference in reporting of ADRs was statistically not significant (P=0.0943). The most common ADRs reported were nausea, anorexia and vomiting. ADRs were most commonly reported when chloroquine was coprescribed.Conclusions:This study indicates that ACT was commonlyused in the treatment of malaria. Results of the analysis suggest that all the ADRs were of moderate intensity and no serious ADR was observed. This baseline information will be useful to implement the ACT in India.

Adverse drug reaction profile of cisplatin-based chemotherapy regimen in a tertiary care hospital in India: An evaluative study

Aims:This prospective study was designed to monitor and analyze the pattern of occurrence of adverse drug reactions (ADRs) to cisplatin-based chemotherapy regimen in the cancer ward of a tertiary care hospital.Materials and Methods:Cancer patients who received cisplatin-based cancer chemotherapy were monitored for adverse reactions. The collected reports were analyzed for demographic and drug details, causality, preventability and severity of adverse effects. Causality was assessed by the World Health Organization (WHO) causality assessment scale and Naranjo's Algorithm. Preventability and severity of ADRs were assessed by modified Schumock and Thornton scale, modified Hartwig and Siegel scale respectively.Results:Among 51 patients, 48 developed ADRs to cisplatin chemotherapy. The reactions observed were nausea, alopecia, anorexia, vomiting, taste alteration, diarrhea, constipation, tinnitus, and hypocalcaemia. The WHO causality assessment scale indicated 69% “possible” and 31% “probable” but no “certain” reactions. Naranjo's Algorithm showed 62% “probable” and 38% “possible” reactions. Most of the reactions belonged to the category of “not preventable”. Reactions like nausea and vomiting belonged to the category of “definitely preventable”. Modified Hartwig and Siegel scale of severity assessment showed that most of the reactions were of “mild level 1” severity except for vomiting, diarrhea and hypocalcaemia, which were of “moderate level 3” severity.Conclusion:Cisplatin-based chemotherapy has a high potential to cause adverse effects. Most of the reactions were of milder nature but not preventable. The common adverse effects such as nausea and vomiting were preventable, but reactions like hypersensitivity reactions and anaphylaxis were not predictable.