Number Of Adverse Drug Reactions Research Articles

Assessing Gender Differences in Neuropathic Pain Management: Findings from a Real-Life Clinical Cross-Sectional Observational Study

Introduction: Neuropathic pain is defined as pain induced by a lesion or disease of the somatosensory nervous system. Pharmacological and non-pharmacological treatments are frequently employed. In the current clinical investigation, we assessed the effects of sex on the safety and effectiveness of medications used to treat neuropathic pain. Methods: We conducted a prospective analysis between 1 February 2021 and 20 April 2024, involving patients with neuropathic pain referred to the Ambulatory of Pain Medicine of “Renato Dulbecco” University Hospital in Catanzaro (Calabria, Italy). Patients over 18 years old with signs of neuropathic pain (Douleur Neuropathique en 4 questionnaire ≥ 4) were included. Exclusion criteria comprised patients with Alzheimer’s disease; patients with nociplastic or nociceptive pain; and patients with neoplasms. Patients with fewer than two accesses to ambulatory care were excluded, as were those who did not sign the informed consent. Clinical data were collected from each enrolled patient and subsequently analyzed, considering clinical outcomes. Sex and gender differences in efficacy were estimated using multivariate linear modeling and propensity-score matching. Results: During the study, 531 patients were screened, and 174 were enrolled (33.5%, mean age 61.5 ± 13.1; 64 males and 110 females, mean age 60.6 ± 13.4 and 61.96 ± 13.0) in accordance with the inclusion and exclusion criteria. Only minor differences in treatment prescription were observed based on age, body mass index, and comorbidities. Smoking, sex, educational level, and body mass index did not induce a significant change in pain perception. Males required slightly higher, though not significantly, doses of drugs for pain control than females. The treatment was not significantly more effective for females than for males. Females did not exhibit a significantly lower number of adverse drug reactions compared to males. Conclusions: The current study found that there are no appreciable differences between the sexes when it comes to the treatment of neuropathic pain.

Experience of using Beers criteria in clinical practice (according to Russian literature)

Objective: analysis of domestic scientific literature to identify ways of applying the Beers criteria, frequency of prescriptions and the structure of potentially inappropriate medications (PIMs) in elderly patients.Material and methods. The search for publications was carried out in Google Scholar abstract database, as wel as in eLibrary and CyberLeninka information-bearing networks for the period from 2013 to 2023. In total, 34 articles were found, among which 18 sources used Beers criteria as a tool for identifying PIMs.Results. In inpatient therapeutic departments, the maximum frequency of PIMs prescriptions according to the Beers criteria was 66.6% of cases, in surgical departments – 70%, in psychiatric departments – 90.4%, and in outpatient treatment settings – 28%. Non-steroidal anti-inflammatory drugs at different diseases were the most prescribed group of PIMs in both inpatients and outpatients. Surgical hospitals took the leading position in prescribing these drugs; specifically, more than 2/3 of elderly patients (75%) received them. According to two studies describing clinical cases of drug-induced falls in patients, the Beers criteria were effective in identifying drugs that can provoke this condition. One of papers presented application of Beers criteria to assess the economic affordability of replacing PIMs with safer new generation drugs.Conclusion. An analysis of domestic literature data has shown various ways of applying the Beers criteria, the frequency of prescriptions, and the most common PIMs. This information will help healthcare workers to be more wary of such drugs and think over applying the Beers criteria in routine practice of geriatric patients, which will further prevent or reduce the number of adverse drug reactions.

A narrative review of theophylline: is there still a place for an old friend?

Theophylline has been used for decades in human medicine for its psychostimulant, anti-inflammatory, and bronchodilator effects. Historically, in pulmonary medicine, theophylline has been used in the treatment of obstructive pulmonary diseases such as bronchial asthma (BA) or chronic obstructive pulmonary disease (COPD). This review aims to determine whether theophylline still has its place in the therapy of obstructive pulmonary diseases or whether we can even extend its use to other diagnoses such as atropine-resistant cardiac arrests, apnea of prematurity, or others. Moreover, we also aim to determine if there is a rationale for using low-dose theophylline due to its immunomodulatory and anti-inflammatory effect, or if the future of methylxanthines lies in newly synthesized derivates of theophylline such as bamifylline, or doxofylline. The narrative review is based on a literature search of the articles indexed in the PubMed database in 2023. We searched the database since the year 2009 using the MeSH terms "theophylline", "aminophylline", and "methylxanthines" and we included original articles in the English language. Theophylline has a number of adverse drug reactions (ADRs), the most serious of which is its effect on the cardiovascular system. It can cause severe arrhythmias or even cardiac arrest when overdosed. On the other hand, there is still a substantial amount of its applications in current clinical practice. There is considerable controversy associated with its use in current medicine, which can be attributed both to its narrow therapeutic range and its mentioned cardiotoxic effect. Herein, we summarize the current state-of-art of theophylline and its use in human medicine.

Improving Drug Safety in Pediatric and Young Adult Patients with Hemato-Oncological Diseases: A Prospective Study of Active Pharmacovigilance.

The acquisition of relevant pediatric clinical safety data is essential to ensure tolerable drug therapies. Comparing the real number of Adverse Drug Reaction (ADR) reports in clinical practice with the literature, the idea of ADR underreporting emerges. An active pharmacovigilance observational prospective study was conducted to assess the safety of oncology pharmacological prescriptions in patients aged 0-24 years at Institute for Maternal and Child Health IRCCS Burlo Garofolo in Trieste and IRCCS CRO National Cancer Institute in Aviano (Italy) between January 2021 and October 2023. Prescriptions and ADRs were evaluated by a multidisciplinary team. A total of 1218 prescriptions for 38 patients were analyzed, and 190 ADRs of grade 3-5 were collected. As compared to historical data, we registered a significant increase (p < 0.001) in the number of ADRs. The risk of ADR was 3.4 times higher in the case of off-label prescriptions compared to on-label ones (OR 3.4; [1.47; 7.89]; p-value = 0.004). The risks of error and near-miss were reported for 6.3% and 18.2% of total prescriptions, respectively. Of the total of 133 interactions, 47 (35.3%) resulted in ADRs. This study shows the importance of pro-active pharmacovigilance to efficiently highlight ADRs, and the fundamental role of multidisciplinary teams (oncologist, pharmacist, pharmacologist, pediatrician, nurse) in improving patients' safety during therapy.

A REVIEW ON PHARMACOVIGILANCE AND DRUG SAFETY MEASURES

Pharmacovigilance, or PV, is the process of continuously monitoring pharmaceuticals once they are put on the market in order to evaluate and enhance their safety profile. Increasing the number of adverse drug reactions (ADRs) that are spontaneously reported is the primary goal in order to collect a wide range of data. The World Health Organization (WHO) defined pharmacovigilance as the science and set of procedures concerning the identification, assessment, comprehension, and rejection of negative effects or problems associated with various drugs in nursing. A clinical test may involve an analysis study involving human subjects in order to address particular health questions. Carefully carried out clinical trials are the fastest and safest methods because they help individuals receive treatments that work and because they improve health. Pharmacovigilance, which provides information on the negative effects that the drug-using population typically experiences, is acknowledged to be essential to the sensible use of pharmaceuticals. Adverse drug reactions (ADRs) are becoming more and more common, and various methods, including scientific and administrative research, in-depth observation, impromptu reporting, and information studies, are being developed with the goal of enhancing pharmacovigilance. Because assessment procedures contain some subjective judgements, integrator reliability is frequently low. In summary, there is presently no well recognized mechanism for assessing casualties from ADRs.

Diverse pharmacovigilance jurisdiction-The right way for global drug safety?

The purpose of this narrative review is to provide a comparison of several countries with different legislation and approaches to pharmacovigilance and to point out how these impact the number of adverse drug reactions (ADRs) that are reported to national competent authorities. Legislative and statistical data regarding ADR reporting from various national competent authorities' websites, databases, and pharmacovigilance centers were used. In combination with the WHO pharmacovigilance quantitative indicator that was applied to evaluate the effectiveness of particular national pharmacovigilance systems in our scope. The study compared pharmacovigilance systems in six countries, focusing on ADR reporting from 2010 onwards. All countries required MAHs to report ADRs, while healthcare professionals' obligations varied. Per-capita ADR reports increased in all countries with available data, with the United States having a significantly higher reporting rate, possibly due to FDA campaigns. Despite starting later, China's per-capita reporting rate surpassed that of the Czech Republic and Japan. The study highlighted various measures taken by countries to enhance ADR reporting systems since the inception of their programs, contributing to the overall increase in reporting rates. ADR reporting is a global priority, with efforts made by different countries to strengthen their pharmacovigilance systems. Some success can be seen in gradually improving per-capita ADR reporting rates. The varying reporting rates and measures taken by each country may serve as a basis for further research and exchange of best practices to improve drug safety monitoring worldwide.

Study on the Relationship Between the Number of Adverse Drug Reactions of Essential Drugs and Visits: Based on Vector Autoregressive Model.

To analyse the relationship between the adverse drug reactions (ADRs) of essential drugs and visits, based on the recorded annual increase in ADRs associated with essential medicines in China, to provide a reliable theoretical basis for further analysis and optimization of the safety of essential drugs. The data of adverse reactions of essential drugs in China from 2011 to 2020, time series analysis was conducted, and vector autoregressive (VAR) model was established. The relationship between the number of ADRs and visits was explored empirically through Granger causality test, impulse response function and variance decomposition. There was a long-term cointegration relationship and one-way causality between the number of visits and ADRs caused by essential medicines. In the initial stage, the ADR response to the number of visits increased sharply, but with an increase in the number of lag periods, the impact remained basically stable, even showing a slight decreasing trend. The number of visits impacts ADRs caused by essential medicines, but this impact remains basically stable after reaching a certain level.

Improving the Documentation of Penicillin Allergy Labels Among Pediatric Inpatients.

Penicillin allergy is the most common medication allergy, and the penicillin allergy label is commonly over-applied without adequate reaction history inquiry or documentation. Because penicillin allergy labels are often applied in childhood and carried into adulthood, we sought to increase the completeness of reaction history documentation from 20% to 70% for pediatric hospital medicine patients and from 20% to 50% for all other pediatric inpatients within 12 months. As a secondary outcome, we also aimed to increase the proportion of delabeling unnecessary penicillin labels to 20% for all pediatric inpatients. To address our aims, our quality improvement initiative included education for pediatric faculty and staff, development and implementation of a clinical pathway for allergy risk stratification, and electronic health record optimizations. Statistical process control charts were used to track the impact of the interventions facilitated by an automated dashboard. Within 12 months of interventions, the completeness of allergy labels improved from 20% to 64% among patients admitted to the pediatric hospital medicine service and improved from 20% to 45% for all other pediatric inpatients. The frequency of penicillin allergy delabeling remained unchanged; however, 98 patients were risk stratified and 34 received outpatient allergy referrals for further testing. The number of adverse drug reactions to penicillin, a balancing measure, did not change during the study period. We increased the completeness of penicillin allergy documentation using a standardized workflow facilitated by a multidisciplinary clinical pathway. With ongoing efforts, more penicillin delabeling in low-risk patients is anticipated.

Gastroprotective therapy in patients with atrial fibrillation receiving anticoagulant therapy: A review

Prevention of thromboembolic complications is the main goal in patients with atrial fibrillation. Anticoagulant therapy is used as prophylaxis, and direct oral anticoagulants are preferred. However, this therapy is associated with a risk of bleeding, among which gastrointestinal bleeding takes a leading place. Proton pump inhibitors are now widely used as prophylaxis for upper gastrointestinal bleedings, but when used long-term, may be associated with a number of adverse drug reactions, including an increased risk of adverse cardiovascular events. Long-term use of these drugs may suppress the action of antiplatelet drugs, disrupt the function of the vascular endothelium, and at the same time cause hypomagnesemia, iron deficiency, vitamin D and K deficiency. At the same time, monotherapy with proton pump inhibitors does not protect against the risk of bleeding from the lower gastrointestinal tract. Thus, as an effective gastro- and enteroprotection, it is necessary to prescribe drugs that protect the gastrointestinal tract throughout its entire length. Such a drug is rebamipide, which has a complex protective effect on the gastrointestinal tract, protecting the mucous membrane at all its levels (pre-, post-epithelial and directly epithelial level), and ensures the restoration of tight contacts in the epithelium of the intestinal tube throughout its entire length. It should be noted that the current consensus documents of the leading experts on the problem of decreasing the risk of gastrointestinal bleedings during direct oral anticoagulant treatment recommend the use of rebamipide for the entire duration of therapy.

A STUDY TO ASSESS, MONITOR, AND REPORTING OF ADVERSE DRUG REACTIONS IN A TERTIARY CARE TEACHING HOSPITAL: HIMS, HASSAN

Objective: An adverse drug reaction (ADR) is an unwanted, undesirable effect of a medication that occurs during usual clinical use. ADR should be quickly identified and managed to limit their detrimental effects on the patient. This study was undertaken to characterize the pattern of ADRs reported through spontaneous reporting system at ADR reporting unit in a tertiary care teaching hospital. Methods: A prospective, observational study was conducted over 3 years between September, 2017 and August, 2019. The ADRs reported were from patients admitted inpatient department of hospital. Evaluation of patient demographics, drug and ADR characteristics, and outcome of the ADRs. Causality and severity assessment was done by the World Health Organization system and Naranjos scale. Results: 82 cases of ADRs were reported during the study period. More number of ADRs was from General Medicine and Pediatric departments, in which the most affected organ systems were the skin and the gastrointestinal tract. The antibiotic classes mostly accounted were cephalosporins. None of the ADR was fatal. Conclusion: ADRs to antibiotics are common and will be resulted in increased health-care cost due to the need of some interventions and increased length of hospital stay. The health-care system should promote proper documentation and periodic reporting to regional pharmacovigilance centers to ensure drug safety.

Analyses of Dupilumab-Related Ocular Adverse Drug Reactions Using the WHO's VigiBase.

Dupilumab is a drug that inhibits the action of interleukin (IL)-4 and IL-13 and is a potent therapeutic drug for allergic diseases such as atopic dermatitis. Although its use has been associated with significant ocular adverse drug reactions (ADRs), the IL-4 and IL-13 inhibition may also have favorable therapeutic effects. The aim of this study was to determine the disease spectrum in which the use of dupilumab may have been associated with an increase or decrease of ocular ADRs. We searched the World Health Organization's VigiBase for ADRs associated with the use of dupilumab for data up to 12 June 2022. The number of all ADRs that were retrieved was compared with the number of ocular ADRs associated with the use of dupilumab. Disproportionate reporting was assessed by calculating the information component (IC) values and odds ratios. Since the introduction of dupilumab, 100,267 ADRs have been reported. Of all the ADRs associated with dupilumab, 28,522 ADRs were ocular complications, and it ranked fourth in the ocular complications by organ level. By assessments of the IC for age ≤ 44years, the most significantly associated ADRs were dry eye followed by blepharitis including eyelid crusting and dryness and conjunctivitis. Crusting and dryness of the eyelids were the most significant ADRs for all age groups. Other ocular ADRs reported include meibomian gland dysfunction, keratitis, glaucoma, and retinal disorders. In contrast, periorbital edema, neuro-ophthalmic disorders, optic neuritis, and macular edema were significantly reduced by the use of dupilumab. Dupilumab-related ADRs included an increase or decrease of various ocular disorders. The results indicate that dupilumab also has potential therapeutic effects.

A CONCEPTUAL STUDY TO EVALUATE THE EFFECT OF POUSHKARADI KASHAYA IN TAMAKA SWASA - BRONCHIAL ASTHMA

TamakaSwasa(Bronchial asthma) is a chronic disorder of Pranavaha Srotas that disturbs daily activities. It is caused by Pratiloma Gati of Vayu supported by Srothorodha produced by Kapha. It is well explained in all the classical texts of Ayurveda. The Udbhavasthana of Swasaroga is said as Amashaya in the classics. Bronchial Asthma, which can be compared with TamakaSwasa is a chronic inflammatory disease of the respiratory tract causing airway obstruction and variable airflow limitation. The prevalance of Asthma has increased over the past 30 years. Asthma is also a complex disease determined by the interaction between genetic and environmental factors. Modern synthetic drugs provide instant relief in these cases but tend to develop a number of adverse drug reactions. As this is a srotorodhavyadhi produced by Vata and Kapha, Drugs which are VataKapha Hara, UsnaVeerya, and VataAnulomana are prescribed in this condition. The polyherbal formulation Poushkaradi Kashaya mentioned in Sahasrayogam, Kashaya Prakarana in SwasakasaAdhikara is UshnaVeerya with KaphaVatha Hara and SwasaKasa Hara properties. Hence it will be effective in removing Kapharodha and causing Vatha Anulomana. Individual drugs in combination likePushkaramoola are antispasmodic, antiinflammatory, and antihistaminic.

Association of Adverse Drug Reactions to HAART with Alcohol Consumption, Herbal Medication and Co-Trimoxazole Prophylaxis among Patients Living with HIV/AIDS in FMC Makurdi, Nigeria

The use of HAART for the treatment of HIV/AIDS infection, despite its success, has been reported to be accompanied by increased number of adverse drug reactions (ADRs) for which some risk factors such as age, gender, co-morbidities have been implicated. The association between alcohol consumption, herbal drug intake and use of co-trimoxazole and ADRs to HAART has not been documented much. The main objective of this study is to determine the association between alcohol consumption, herbal drug intake, use of co-trimoxazole and presentation of ADRs to HAART in HIV/AIDS patients in Makurdi where there’s high HIV infection, alcohol consumption and herbal use. It was a combination of prospective and retrospective study at FMC, Makurdi. We used clinical records of the patients and questionnaires for patients enrolled from January to October, 2019 and followed up for six months. The biodata, drug history including herbal medications and social life (use of alcohol) history were retrieved. A total number of three hundred and three (303) patients were recruited during the study period out of which two hundred and ten (210) patients were used. From a total of 210 patients, 144 (68. 6%) were females while sixty-six, 66 (31.4 %) were males. Of these, only 68(32.4%) patients took alcohol while 89 (42.4%) patients used herbal medications together with HAART regimen and 185(88.1) were on cotrimoxazole prophylaxis. 22 patients presented with ADR with peripheral neuropathy and insomnia being the commonest ADRs. 54.5% (majority) of the patients with ADRs took alcohol while 81.8% (majority) of the patients who developed ADRs were actually on herbal medications or co-trimoxazole. The p-value&gt;0.05. Alcohol consumption, herbal medication use and co-trimoxazole prophylaxis in HIV/AIDS positive patients while on ARVs may increase ADRs to ARVs. Thus, HIV/AIDS patients should be discouraged from use of alcohol and herbal medication while on HAART.

443 Selection of Outcome Measurement Instruments for a Core Outcome Set for trials aimed at improving appropriate polypharmacy in older people in primary care

Abstract Introduction Different outcome measurement instruments (OMIs) have been used to measure similar outcomes in intervention studies focusing on improving appropriate polypharmacy in older people (1). It is crucial to reach consensus on which OMIs should be used for each outcome in a core outcome set (COS) to promote synthesis of trial findings and help identify effective interventions. A polypharmacy COS was previously developed, consisting of seven outcomes, including serious adverse drug reactions (ADRs), medication appropriateness, falls, medication regimen complexity, quality of life, mortality and medication side effects (1). To date, there has been no consensus as to which OMIs should be used for these outcomes. Aim To select OMIs for the seven outcomes in the COS developed to improve appropriate polypharmacy in older people in primary care. Methods This study followed the COSMIN (Consensus-based Standards for the selection of health Measurement Instruments) initiative’s guidelines for selecting OMIs for a COS (2), which include finding existing OMIs from a systematic review, conducting a quality assessment of the OMIs, selecting one OMI for each outcome in the COS, and running a Delphi consensus survey (two rounds) on OMIs for each outcome. For the Delphi exercise, researchers focusing on care of older people or clinicians who had experience in prescribing for this population in primary care, together with public advocates for older people were invited by email to participate. Following provision of consent, a questionnaire was developed and distributed by the SoGoSurvey® platform on two occasions. The two rounds were distributed on June 21st 2022 and July 11th 2022, respectively. Each round remained open for 14 days to allow participants to take part in the study. The questionnaire comprised a list of seven OMIs along with their definitions and illustrative examples. Stakeholders were asked to choose one option (‘agree’, ‘disagree’ or ‘unsure’) for every OMI. Response rate and distribution of scores for the seven OMIs were calculated following each round. Consensus for the inclusion of an OMI in the COS was reached if 70% or more participants selected ‘agree’ and 15% or less participants selected ‘disagree’. Results One hundred and eighty-eight emails were sent to relevant stakeholders (176 researchers or clinicians, 12 public representatives) inviting them to take part in the study. Fifty-seven (30.32%) stakeholders (56 researchers and one public representative) agreed to participate. Fifty (87.72%; all participants were researchers or clinicians) completed Rounds 1 and 2 of the Delphi survey. Following Rounds 1 and 2, consensus (≥70% participants agreed) was reached for three OMIs – ‘the number of ADRs’ (98%), ‘the number of deaths’ (76%) and ‘the number of patients who fell’ (70%) – to measure the ‘serious ADRs’, ‘mortality’ and ‘falls’ outcomes, respectively. Consensus was not reached for the remaining four OMIs. Conclusion This study led to the selection of OMIs for outcomes in a COS aimed at improving appropriate polypharmacy in older people. Although this study planned to include public participants, none agreed to participate. Future work should determine the most appropriate OMIs for the other four outcomes in the COS.

Adverse reactions of high-osmolar and low-osmolar radiographic contrast media in clinical practice

Introduction . Adverse drug reactions (ADR) to administration of radiographic contrast media (RCM) are observed in 10–20 % of patients. Individual tolerability of drugs is affected by RCM properties (ionicity, osmolarity). Aim . Evaluation of ADR in patients during diagnostic studies using high- and low-osmolar RCM. Methods . Analysis of 52 reports of adverse reactions to RCM registered in medical organizations of Voronezh region in 2014–2021 was performed. Group 1 included 21 patients with ADR to high-osmolar RCM (sodium amidotrizoate, yoxitalamic acid), group 2–31 patients with ADR to low-osmolar drugs (yogexol, yopromide, yopamidol, yoversol). Results . Age of patients is 6–82 years, median 48.5 years, children — 8 persons (15.4 %), women — 31 patients (59.6 %), serious reactions — 28 (53.8 %). Since 2017 there has been an increase in the number of ADRs with constant frequency of serious reactions. In 2020–2021 ADRs to low-osmolar drugs were mainly registered. Life-threatening conditions (anaphylactic shock, arterial hypotension, arrhythmia) were observed in 70.2 % of group 2, in 28.6 % of group 1 (p=0.007). One patient with initial renal dysfunction and comorbid pathology was reported to develop nephrotoxicity to yogexol. Pharmacological correction was performed in 92.3 % of cases. In 57.7 % of the patients ADR ended in recovery, in the other cases — state improvement. Conclusion . Side effects of high-osmolar and low-osmolar RCM mainly had form of hyperergic reactions of immediate type and were reversible. High frequency of serious reactions to lowosmolar RCM against an increase in their use requires a more careful selection of patients for X-ray contrast studies.

Therapeutic physical factors in treatment programs for patients with chronic pancreatitis

The purpose of the study is to study the effectiveness and safety of using therapeutic physical factors in rehabilitation treatment of patients with chronic pancreatitis in hospitals. Material and methods. There has been carried out an open randomized controlled trial which included 95 patients with chronic biliary pancreatitis of stage II-III, moderate severity, in the stage of exacerbation, not requiring surgical treatment. Two groups were formed by simple randomization. The patients of the control group (n = 46) had stationary treatment in accordance with Russian clinical guidelines; in the main group (n = 49) the patients were prescribed low-mineralized mineral water in the form of ingestion and electrophoretics according to the mitigated methods in addition to the treatment complex. Results. The inclusion of low-mineralized sulphate-hydrocarbonate calcium-sodium mineral waters in the treatment complex of patients with chronic pancreatitis in hospitals, their ability to enhance pharmacological potential of the used drugs at the stationary stage provided a significant reduction of clinical and ultrasound indicators with 76.56% of the patients at reduction of pain syndrome in 3.56 (p < 0.01) times, diarrhea - 1.94 (p < 0.01), decrease in enzymatic activity - 3.16 (p < 0.01), acute-phase blood values - in 3.14 (p < 0.01), improvement of metabolic status - in 2.29 (p < 0.01) times. This helped to reduce the length of stay in a 24-hour hospital by 2.7 days, reliably significant in comparison with the data in the control group based on the treatment in accordance with Russian clinical recommendations. In addition, a comparable number of adverse drug reactions were detected in both groups (8.13% verses 10.63%), which indicates equal safety of the used medical technologies. Conclusion. Inclusion of therapeutic physical factors in the complex of treatment of patients with chronic pancreatitis in hospitals provides reliably significant increase of therapeutic measures effectiveness.

PS-C19-5: SAFETY PROFILES OF SACUBITRIL/VALSARTAN IN EARLY POST-MARKETING PHASE VIGILANCE FOR THE INDICATION OF CHRONIC HEART FAILURE AND HYPERTENSION

Background: The objective was to investigate and report the safety profile of Sacubitril Valsartan Sodium Hydrate (Sacubitril/Valsartan) (Entresto®) in Early Post-marketing Phase Vigilance (EPPV). Methods: In accordance with the regulation, the 6-month EPPV was conducted for the physicians or pharmacists at all medical institutions to which the drug was delivered. Safety information was collected and tabulated for the indication Chronic Heart Failure (CHF) (August 26, 2020 - February 25, 2021) and Hypertension (September 27, 2021 - March 26, 2022). The adverse drug reactions (ADRs) were classified using the basic terms of Medical Dictionary for Regulatory Activities (MedDRA). In addition, we focused on the five risks (hypotension, renal dysfunction/renal failure, hyperkalemia, angioedema, and dehydration) listed as Safety Specification in the Risk Management Plan (RMP). Results: The estimated number of patients treated with Sacubitril/Valsartan for the indication of CHF and hypertension was 24,898 and 165,000 during the data collection period. The number of ADRs were confirmed to be 850 (345 serious) for CHF and 455 (84 serious) for hypertension. No new safety findings were identified in both EPPVs. For both indications, the most common RMP-related ADRs were hypotension-related ADRs that occurred within 30 days after initiation were 87 (162 had, followed by renal dysfunction-related ADRs. Furthermore, hypotension-related ADRs were 268 (75 serious) for CHF and 93 (three serious) for hypertension. Hypotension-related ADRs that occurred within 30 days after initiation were 87 (162 had an unavailable date of onset) for CHF and 19 (71 had an unavailable date) for hypertension. Regarding renal dysfunction-related ADRs, the number of ADRs were 45 (45serious) for CHF and 19 (19serious) for hypertension. Renal dysfunction-related ADRs that occurred within 30 days after initiation were 17 (23 had an unavailable date of onset) for CHF and three (14 had an unavailable date) for hypertension. The number of hyperkalemia-related ADRs, angioedema, and dehydration were 35 (including 19 serious), five (five serious), and 25 (two serious) for CHF, and nine (five serious), four (four serious), and four (sero serious) for hypertension, respectively. Conclusion: No new safety findings were identified during the 6-month EPPV. Furthermore, there were no differences in safety profile by indication.

Pharmacovigilance: Study of pattern of adverse drug reactions at a tertiary care teaching hospital, Aurangabad, and Maharashtra, India: A prospective study and forthcoming challenge for the future

Background: Reporting adverse drug reaction (ADRs) through Pharmacovigilance program of India is very important for effectiveness of drug treatment. It allows professionals to detect, assess, monitor and derive ways to reduce the incidence of ADRs. Aims and Objectives: The aim of the study was to study the patterns of ADRs reported in a tertiary care teaching hospital. Material and Methods: This study was conducted for a period of 10 months. We included all the forms of ADRs caused by drugs which were sent to the Pharmacovigilance cell, Department of Pharmacology. The reports were analyzed for age group, anatomical therapeutic classification, organ system involvement, type, severity, and the causality assessment. Results: A total of 104 ADRs form were analyzed. The highest percentage 59.6% of ADRs was seen in 19–59 years of age group. Females were reported more reactions. The most common class of drugs involved was antimicrobial agents (51.9%). Major organ system affected was skin constituted a major component (73.0%). Our study showed that 75% reactions were predictable while 13.4% were unpredictable reactions. About 51.9% of reactions were moderate according to severity grading. The WHO causality assessment showed that 37.5% reactions were probable/likely and 32.6% were possible. About 75.9% of patients suffered from temporary harm and require intervention while 17.3% requires hospitalization. About 53.8% of reactions were from definitely preventable category and 43.2% were probably preventable. Conclusion: The results suggest that staff of our hospital is reporting ADR according to the guidelines. There will be increase in spontaneous reporting and decrease in number of ADRs with further reinforcement. The data generated from Pharmacovigilance department will also help in finding ways for safer use of drugs in our hospital.

ADR profile among healthcare workers on Hydroxychloroquine prophylaxis in a tertiary care teaching hospital in India

Background: WHO has declared Coronavirus 2019 (COVID-19) as pandemic on 11th March 2020. Hydroxychloroquine (HCQ) chemoprophylaxis has been approved by the Indian Council of Medical Research (ICMR) for asymptomatic healthcare workers treating suspected or confirmed COVID-19 cases and asymptomatic household contacts of confirmed patients. However, there is a scarcity of data regarding the efficacy and safety of HCQ for COVID-19 prophylaxis and treatment. Objective: The present study was designed to evaluate the adverse drug reaction (ADR) profile of HCQ prophylaxis among healthcare workers in a tertiary care teaching hospital in India. Methods: A Descriptive cross-sectional study was conducted in Kalpana Chawla Medical College and Hospital, Karnal for duration of 3 months (April-June 2020). The study was performed on the reported ADRs due to HCQ prophylaxis by the healthcare workers to the ADR monitoring centre of the institute during this period. Results: Gastrointestinal disturbance such as loose stool (16.4%) and hyperacidity (14.9%) were the most commonly reported ADRs during the study period. The incident rate of adverse drug reactions was 23.7%. The number of ADRs was found to be significantly (p&lt;0.01) more in female as compared to male. We have observed that most of the reactions were reported following the 1st day loading dose. Conclusions: Our results showed that gastrointestinal system was most commonly affected. Loose stool and hyperacidity were most frequently reported ADRs due to HCQ prophylaxis. Larger studies are required to ensure the safety of the use of HCQ as prophylaxis for COVID 19.

Dapagliflozin and euglycaemic diabetic ketoacidosis – ‘But doctor my sugars were normal!’

Dear Editor, A ‘Dear Doctor Letter’ was issued by the manufacturer of Forxiga (dapagliflozin) in November 2021; this followed reviews by the European Medicines Agency and the UK Medicines and Healthcare products Regulatory Agency. The letter stated that ‘The removal of the T1DM indication is not due to any safety concern for dapagliflozin in any indication, including T1DM’ but must be discontinued ‘in patients with T1DM by or in consultation with a physician specialised in diabetes care and be conducted as soon as clinically practical.’1 Dapagliflozin was previously approved in the treatment of diabetes for combination with insulin therapy in type 1 diabetes and with oral medications and insulin in type 2 patients. The pathogenesis of EuDKA occurs as a consequence of absolute insulin deficiency leading to reduced glucose utilisation and enhanced lipolysis; increased delivery of free fatty acids (FFAs) to the liver coupled with raised glucagon levels promotes FFA oxidation, and subsequent production of ketone bodies.2 Rosenstock and Ferrannini also reported that following a US FDA safety communication, the majority of reports of EuDKA between 2014 and 2015 in the US were actually in patients with type 2 diabetes.2 The UK Yellow Card report did not specify the type of diabetes. A review of the UK MHRA Yellow Card reporting system on dapagliflozin in October 20223 showed the following results: total number of adverse drug reactions (ADRs) reports, 2155; serious ADR reports, 1371; fatal ADR reports, 26 (cut-off 31 August 2022). Details of ADRs which could be related to EuDKA are shown in Table 1. The number of reports submitted had risen following the letter from the manufacturer. It is expected that a large number of these reports could be related to the concomitant use of dapagliflozin and insulin therapy in patients with type 2 diabetes. Appropriate monitoring and awareness on the part of health care professionals and patients are necessary to prevent potentially harmful and fatal consequences. The advice from both the manufacturer and the medicines regulatory agencies surrounding the actions required in patients with type 1 diabetes is clear and we may prevent problems by close monitoring of patients in diabetes specialist units. Such task is facilitated by the use of electronic medical records and access to the list of all medications used by these patients. Following the research findings on the occurrence of EuDKA in patients with type 2 diabetes, we may argue that these patients should also be included in a review for EuDKA. From personal and documented reports, patients with type 2 diabetes often react negatively to the introduction of insulin therapy to their medications.4 Part of the rationale to include insulin therapy usually includes improved glycaemic control. Following a period of improvement in their self-monitored blood glucose, some patients might react by stopping or reducing their use of insulin. The resulting ketonaemia in patients with insulin deficiency taking SGLT2 inhibitors is initially asymptomatic or clinically undetectable and could gradually lead to severe ketoacidosis. There are data which document the increased incidence of chronic heart failure, especially in people with type 2 diabetes;5 as this diagnosis is also included in the newer indications for dapagliflozin it will be important to communicate the association of EuDKA and dapagliflozin use to specialists who might not necessarily be expert in managing this complication of diabetes. Most patients with type 2 diabetes are managed in primary care and initiating a community-wide alert would take time to complete and require significant human resource, increased budget, and likely lead to increased patient anxiety. Blood tests to detect low endogenous insulin secretion would also take time and increased resources. A more rapid and simple approach is required. One option could be to request that all patients with long-standing type 2 diabetes who are treated with insulin in combination with dapagliflozin or any other SGLT2 inhibitors should be advised to use blood or urine ketone testing to detect EuDKA, particularly when insulin doses are being reduced or withdrawn. Awareness of these such parameters would help health professionals to quickly identify and treat patients at risk. The Association of British Clinical Diabetologists and Diabetes UK have produced joint guidance on communication and education requirements to be provided to patients who were prescribed an SGLT2 inhibitor for the first time.6 This provides useful and practical suggestions for minimising adverse reaction to the use of these medicines. Michael Stacey, MD, FRCP, Senior Lecturer, Royal Centre for Defence Medicine, UK There are no conflicts of interest declared.