Health Organization Causality Assessment Scale Research Articles

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.

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.

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.

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.

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.