Current Drug Safety - Volume 17, Issue 4, 2022

Individuals suffering from mental illnesses, unfortunately, have a shorter lifespan. An increase in mortality rates is primarily due to physical illness, unhealthy lifestyle, and associated comorbidities. Antipsychotic medications, previously known as tranquilizers, antipsychotics, or neuroleptics, can alleviate or attenuate symptoms related to psychosis, delusion, and/or hallucinations and are used in the treatment of psychosis, schizophrenia, bipolar disorder, depression, or Alzheimer's disease. Within hours to days, these medications alleviate symptoms and reduce confusion in individuals with psychosis; however, the full effect may take longer than usual in some cases. Importantly, these drugs do not cure the disease, but only treat the symptoms of the disease. The treatment is adjusted to reduce any psychotic symptoms while keeping the adverse effects to a minimum level. Antipsychotics may lead to increased risk of diseases, including but not limited to, diabetes, obesity, metabolic disorders, cardiovascular, renal, or respiratory disorders. Improved dosages, polypharmacy, and age-specific treatment play an important role in limiting the comorbidities, as well as the side effects. Further research and clinical attention are required to understand the functioning of these medications. The review focuses on the use of antipsychotic medications in different diseases and their effect on mental health.

Background: Thiazolidinediones are potent exogenous agonists of PPAR-γ that augment the effects of insulin to its cellular targets, mainly at the level of adipose tissue. Pioglitazone, the main thiazolidinedione in clinical practice, has shown cardiovascular and renal benefits in patients with type 2 diabetes, durable reduction of glycated hemoglobulin levels, important improvements of several components of the metabolic syndrome, and beneficial effects of non-alcoholic fatty liver disease. Objective: Despite all of its established advantages, the controversy for an increased risk of developing bladder cancer, combined with the advent of newer drug classes that achieved major cardiorenal effects, have significantly limited its use spreading a persistent shadow of doubt for its future role. Methods: Pubmed, Google, and Scope databases have been thoroughly searched, and relevant studies were selected. Results: This paper thoroughly explores both in vitro and in vivo (animal models and humans) studies that investigated the possible association of pioglitazone with bladder cancer. Conclusion: Currently, the association of pioglitazone with bladder cancer cannot be based on solid evidence. This evidence cannot justify its low clinical administration, especially in the present era of individualised treatment strategies. Definite clarification of this issue is imperative and urgently anticipated from future high quality and rigorous pharmacoepidemiologic research, keeping in mind its unique mechanism of action and its significant pleiotropic effects.

Aims: The study aims to raise medical specialists’ awareness regarding the severity of possible complications of levamisole administration, and demonstrate the role of accurate medical history collection in a differential diagnosis. Background: Levamisole, an anthelmintic drug with immunomodulatory effects, has long been used worldwide till the early 2000s, when its association with demyelinating leukoencephalopathy was established. However, in the developing countries, it is still widely used for the prevention and treatment of helminthic invasion in humans. The actual prevalence of levamisole-induced multiple inflammatory leukoencephalopathy (LEV-induced MIL) in Russia remains unknown, and therefore, the study of its frequency and characteristics is indisputably important. Objectives: The objective of this study is to determine the clinical features and MRI findings of levamisole- induced MIL in the Russian population, and to analyse the frequency of diagnostic errors at the initial assessment. Methods: A single-center retrospective analysis of total 30 patients who were diagnosed with LEV- induced MIL and attended the Research Center of Neurology was conducted. Inclusion criteria were 1) clinically: acute or subacute polysymptomatic onset of neurological disturbances, 2) MRI: multifocal demyelinating lesion with no evidence of dissemination in time, 3) anamnestic data: levamisole exposure from 2 to 8 weeks before symptoms onset as well as monophasic disease course (absence of relapses according to follow up assessments up to 3 years). Results: Clinically, presentation with constitutional symptoms including headache, fever, fatigue and myalgia, focal motor disturbances and dysarthria prevailed in our cohort. On the brain MRI, multiple foci of demyelination with simultaneous gadolinium enhancement were observed. The link between neurological symptoms and levamisole intake has often been detected only during follow- up assessments. Patients were most often misdiagnosed with acute disseminated encephalomyelitis, stroke and multiple sclerosis. In most cases, LEV-induced MIL was successfully treated with intravenous corticosteroids and/or plasma exchange (PLEX), however, residual neurologic symptoms were preserved in some patients. Additionally, two detailed clinical cases of patients being initially misdiagnosed are presented in the article. Conclusion: The differential diagnosis remains difficult for suspected cases of LEV-induced MIL that could lead to delayed therapy initiation, and consequently incomplete recovery. Growing evidence suggests that a single administration of levamisole even in low doses might potentially lead to severe neurological deficit or death. Therefore, changes in medication management policies are required in order to prevent the uncontrolled use of levamisole.

Background: The reports on adverse experiences following vaccination are scanty from India. It is important to know the real-world post-vaccination experience outside of clinical trial conditions. Objectives: The study aims to estimate the incidence of adverse events following immunization with the ChAdOx1 nCoV-19 coronavirus vaccine and to identify the predictors for the development of vaccine adverse events. Methods: A prospective observational study was conducted among health care workers who received the ChAdOx1 nCoV-19 coronavirus vaccine. Study participants were monitored at the site for 30 min following vaccination and were followed up for 7 days after receiving the second dose, with a purpose-specific designed online surveillance form to enquire about any adverse events following vaccination. We used the Chi-squared test for categorical variables and multivariate regression analysis to identify predictors for the development of vaccine adverse effects. Results: Of 411 participants, the mean age was 30.77 ± 12.5 years and 76.2% were females. Overall, 207 (50.4%) respondents reported at least one post-vaccination symptom receiving either dose of coronavirus vaccination. Fever (34.8%), local pain at the injection site (28.0%), tiredness (25.5%), chills (20%), myalgia (18.7%), headache (17.8%), injection site stiffness (5.4%), joint pain (4.6%) and nausea-vomiting (3.8%) were the most prevalent symptoms following the first dose. Adverse reactions reported after the second dose were milder and less frequent. Postvaccination symptoms were more likely in the younger age group, those with comorbidity particularly, bronchial asthma , and a history of allergy to food/drugs. Conclusion: All the adverse reactions were of a minor type and non-serious. Side effects were less common in older adults (>60 years). Reactions to the second dose were lesser in intensity and frequency. Younger age, history of allergy, and comorbidities, particularly asthma, were found to be major predictors for the development of adverse events and require more watchful vaccine administration.

Background: Chemotherapy has high efficacy, but it is associated with several adverse drug reactions (ADRs). Objectives: A retrospective observational study to explore the prevalence, causality, and preventability of ADRs of anticancer agents was conducted. Methods: The study was carried out at Punjab Institute of Medical Sciences Jalandhar, Punjab after obtaining IEC approval. The data was collected from cancer patients undergoing treatment at the hospital. The causality assessment of the collected data was done by using WHO causality assessment criteria. The preventability and severity of the reported ADRs were also assessed. Results: From 50 medical records, a total of 47 ADRs were recorded among 25 patients, out of which 16 were females and the rest were males. The cancer cases observed were breast carcinoma, leukaemia, lung, colon, and ovarian cancer. The highest number of ADRs were observed with alkylating agents, followed by taxanes, antimetabolites, kinase inhibitors, and monoclonal antibodies. The most affected organ systems were the gastrointestinal system, blood, and lymphatic system. According to the causality assessment, the majority of the ADRs were of the "possible" category. Preventability analysis showed that 85.11% of ADRs were unavoidable reactions, while 14.89% of ADRs were possibly avoidable. Severity analysis of ADRs showed that 87.23% of ADRs were mild and 12.77% were of moderate severity. The majority of the ADRs were unavoidable and mild to moderate in severity. Conclusion: Since the majority of the ADRs were of the unavoidable category, it indicates that the treatment regimens are acceptable as per the current clinical management of cancer patients.

Background: Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV). Though many classes of drugs have been advocated/used for the treatment of this disease, vaccines are being targeted for its ultimate prevention. Indian Government has approved Covishield (ChAdOx1 nCoV19 Corona Virus Vaccine-Recombinant) for restricted use in emergency circumstances. Objective: This study is aimed at evaluating the safety profile of the Covishield vaccine among healthcare workers in a tertiary care hospital. Methods: All Adverse Drug Reactions (ADRs) reported to the ADR monitoring centre by healthcare workers who received the Covishield vaccine during the study period of 3 months were analysed on various parameters, and the assessment was done using the WHO-UMC scale. Results: During the study period, a total of 1216 beneficiaries were vaccinated with 1st dose of Covishield, and out of these, 727 beneficiaries also received 2nd dose of the vaccine. Out of the 1216 beneficiaries vaccinated, 69 ADRs were reported in 24 healthcare workers. The most common ADR reported was fever (24.64%), followed by myalgia (18.84%). No death or any serious anaphylactic reaction was observed. None of the healthcare workers experienced any adverse event during the observation period of 30 minutes. Serious reactions were reported in 4 healthcare workers as per the Pharmacovigilance Programme of India (PvPI) criteria of serious AEFI. 92% of healthcare workers recovered from ADRs during the study period. 84% of ADRs were classified as probable as per the WHO-UMC scale. Conclusion: As per the Government of India directives, all the healthcare workers in the institute were encouraged to take both doses of the Covishield vaccine. The beneficiaries were kept under observation for 30 minutes and monitored for any adverse drug reaction following vaccination. The vaccine was found to be safe with a very low incidence of ADRs.

Background: The Japan Pharmaceutical Association has conducted drug event monitoring to detect drug events related to pemafibrate. As there are a few studies on the safety of pemafibrate in clinical settings, a pilot study evaluating the association between drug use and detected events was performed in Japan. Aims: In this study, the association between detected events and the use of pemafibrate, utilizing pharmacy records maintained by community pharmacists, was investigated. We identified the newuser cohort using a test and active comparison drug and collected the baseline information. An active comparison group comprising new users was used to assess the events. Methods: A retrospective cohort study using questionnaires regarding baseline and event data was conducted by community pharmacists belonging to the Japan Pharmaceutical Association. The incidence of event and estimated hazard ratio were calculated using the Cox proportional hazards model that was adjusted for confounding factors, such as age and sex. Results: A total of 1294 patients using pemafibrate and 508 patients using fenofibrate were identified as new drug users. The most reported events involving suspected adverse reactions and add-on drugs were increased blood pressure and lipid-lowering effects with pemafibrate use, and nasopharyngitis, pruritus, dizziness, and lipid-lowering effects with fenofibrate use. No significant differences were found in commonly occurring events, except that an add-on anti-hypertensive drug has been used by pemafibrate users compared to fenofibrate users. Conclusion: This study conducted by pharmacists can facilitate the safety assessment of newly marketed drugs, as few drug use investigations with a comparator are carried out by the Japanese authority for pharmaceutical companies. However, further research is required.

Background: Adverse events are a major threat to any immunization programs, which have proven to be a boon for developing nations like India. Hindering factors, such as inadequate knowledge, inappropriate attitude, incorrect practices, etc., of the guardian affect the vaccination rate. Aim: This study aims to assess the effectiveness of clinical pharmacist intervention on an adverse event following immunization in the pediatric population receiving immunization. Methods: Pediatric subjects <5 yrs of both genders receiving immunization in a tertiary care hospital during the period of 8 months were considered. Subjects were randomized into control and interventional groups. Pharmaceutical intervention was done in interventional group in the form of patient counselling, and a patient information leaflet. Adverse event following immunization was recorded and analysed for both groups along with Knowledge, Attitude, and Practice scores of guardians’ pre and post intervention through customized data collection forms. Microsoft excel and statistical software SPSS IBM version 22 was used to analyse the data. Results: The study was conducted on a total of 88 subjects (n) in which 79 were <2 years, 1 and 8 were between 2-4 years and 4-5 years, respectively. Forty-nine subjects (55.69%) were female, while 39 were male (44.31%) with a response and completion rate of 91.66%. 97.7% of subjects received Bacillus Calmette-Guerin vaccination (majority), while 8.88% received pneumococcal special vaccine (minority). Adverse event following immunization was recorded in 31(35.22%) cases. Knowledge, Attitude and Practice scores increased by 42.17%, 52% and 12.67%, respectively in guardians after clinical pharmacist intervention. Conclusion: This study demonstrates that educational inputs, awareness programs, and proper medical professional intervention can act as a helping factor to fight against AEFI and towards the success of an immunization program.

Background: Zinc supplementation is frequently prescribed during the treatment of COVID-19. However, the evidence supporting the efficacy of this intervention is mixed. Objective: Establish the clinical utility of zinc supplementation to alter disease severity in COVID- 19 illness. Methods: We performed a multicenter, retrospective, observational chart review of patients admitted to Ascension St. John Hospital or Detroit Medical Center from January 1st, 2020 to May 31st, 2020. All included patients received concomitant hydroxychloroquine due to its zinc ionophore activity. Our primary outcome was a change in Sequential Organ Failure Assessment (SOFA) score with secondary outcomes including all-cause mortality, need for intubation, and QTc prolongation as a safety outcome. Results: We identified 489 patients who received zinc and 587 patients who did not. The primary outcome showed a small difference in the change in SOFA score in patients receiving zinc in univariate analysis (1.08 vs. 1.43, p=0.02), but this difference was not significant after adjustment for confounding factors such as receipt of corticosteroids and ICU admission. Mortality was not different between those that received zinc compared to those that did not (32.7% vs. 35.9%, p=0.268). Conclusion: Our retrospective study, including 1064 patients hospitalized in Detroit, demonstrated no differences in mortality or disease severity with zinc combination. Furthermore, prospective studies are needed to establish the utility of zinc in the treatment of COVID-19.

Background: Hydroxychloroquine (HCQ) has been extensively used during the COVID-19 pandemic both as a therapeutic and prophylactic drug. HCQ is generally well tolerated; however, adverse drug reactions (ADRs) in COVID-19 need further exploration. In this study, we have determined the type and pattern of ADRs of HCQ as a prophylactic and therapeutic drug in COVID-19. Methods: All spontaneous suspected ADR reports due to HCQ in COVID-19 patients submitted to the ADR monitoring of a tertiary care hospital were included. Additionally, a survey was designed for active surveillance of ADRs among healthcare professionals (HCPs) who were on prophylaxis with HCQ. The ADRs were analyzed to determine severity, causality, and preventability using the Hartwig Scale, World Health Organisation-Uppasala Monitoring Centre (WHO–UMC) scale, and modified Schumock and Thornton criterion respectively. Results: Sixty-four ADR reports were received from COVID-19 patients. A total of 78 ADRs were reported by 49 HCPs who were on HCQ prophylaxis. The majority of the patients had ADRs related to skin and soft tissues (37.5%), whereas the HCPs on prophylaxis mostly had gastrointestinal complaints (42.3%). ADRs observed in HCPs on prophylaxis were mild, not requiring any intervention. However, 50% of ADRs in patients were of “moderate” category. Conclusion: Undiscerning and unsupervised use of HCQ can expose the general population as well as patients to serious adverse drug effects. Utmost care is necessary before using HCQ prophylactically or for treatment in COVID-19.

Background: Medication errors are a reality in all settings where medicines are prescribed, dispensed, and used. High-alert medications (HAM) are those that bear a heightened risk of causing significant harm to the patient if used erroneously. Though mishaps with HAM may not be more common than with other drugs, the consequences of error with them can be especially serious. We conducted a survey on knowledge, attitude, and practice, among residents working in a teaching hospital to assess the ground situation regarding HAM awareness and handling. Methods: We approached 492 residents among the approximately 600 currently working through purposive sampling. Residents in all disciplines (clinical, paraclinical, and preclinical) were targeted. A structured questionnaire with 54 questions, pilot-tested on 20 volunteer residents, was used for data collection. The questionnaire was administered to residents through face-to-face interviews by two raters while they were on duty, but not during rush hours. Results: Of the total 261 responses received, 32.33% respondents correctly defined or explained the meaning of the term ‘medication error’. Knowledge regarding the difference between medication error and adverse events did not get reflected in 68.38% of the participants, and only 16.86% were able to name the relevant group of medicines as HAM. Regarding attitude in dealing with HAM, the majority believed that taking the history of drug allergy and reconciling all prescription and over-the-counter (OTC) drugs already being used before prescribing or using medicine is important. In practice, most respondents followed protocols but not routinely. Several potential errors in practice were identified. Conclusion: The current situation requires corrective action. There is an urgent need for improving awareness regarding HAM for the sake of patient safety. The pharmacology department can take the lead in designing awareness campaigns with support from the hospital administration.

Background: The emergence of coronavirus SARS-CoV-2, and the subsequent global epidemic of COVID-19, brought with it innumerable new clinical experiences across all medical specialties, and psychiatry is no exception. Individuals with serious mental illness, in particular schizophrenia and related disorders, may be especially susceptible to coronavirus infection given the overlapping risk factors of vulnerable sociodemographic status, increased challenges with quarantining requirements, and limited compliance with “respiratory etiquette.” The case presented here describes a patient with schizophrenia who was being managed on clozapine and who developed symptomatic COVID-19 infection. Special care was taken to ensure that potential interactions between clozapine and the associated COVID-19 treatments were safe for the patient’s mental and physical wellbeing. Case Presentation: A 71-year-old schizophrenic Caucasian male is being managed with clozapine. While hospitalized, the patient was screened positive for COVID-19 and was admitted to the ICU due to his declining respiratory status. He was treated with both remdesivir and prednisone. He was able to fully recover from his COVID-19 infection. Conclusion: The authors review the clinical characteristics of the case, highlighting both the overlapping synergistic effects and antagonistic influences of clozapine therapy in combination with COVID-19 and its associated treatments. A review of the literature offers an opportunity to examine various frameworks for individualized clinical decision-making while making the case for greater epidemiologic research into the optimal management of individuals with a psychotic disorder who are diagnosed with COVID-19 infection.

Background: Valproate is a widely prescribed medication for the control of seizures in the pediatric population. It has been reported to be an important implication for drug induced pancreatitis. A case of valproate induced acute pancreatitis operated as surgical abdomen has been reported here. Case Report: A 13-year-old child presented to the emergency department with severe pain and abdominal distension associated with vomiting and constipation for four days. The patient’s caregivers did not disclose any medication history. Based on clinical examination and ultrasonography that revealed mild free fluid, a provisional diagnosis of pyoperitoneum with peritonitis was made. An emergency exploratory laparotomy was undertaken during which acute pancreatitis was diagnosed intra-operatively. On further enquiry, the caregiver revealed the history of valproate intake for the last six months for generalized tonic-clonic seizures. Valproate was discontinued and there was complete resolution of symptoms. Conclusion: Both clinicians, as well as caregivers of paediatric patients receiving valproate, should be watchful regarding this possible life-threatening complication to avoid delay in diagnosis and appropriate management.

Introduction: Psoriasis is a chronic inflammatory skin disease requiring long-term treatment. However, there are approximately 71 million individuals with chronic HCV infection worldwide. In psoriatic patients affected by chronic HCV infection, conventional systemic drugs may be frequently contraindicated, while data on biologics use are limited. Case Presentation: The case of a 48-year-old Caucasian man suffering from a severe form of plaque psoriasis and affected by a chronic-HCV-infection treated with guselkumab has been reported. Despite a huge improvement of the skin lesions (PASI reduced from 18 to 2), guselkumab was discontinued due to an HCV-infection reactivation after 3 months of treatment. Conclusion: To the best of our knowledge, this is the first case report of the use of guselkumab in an HCV psoriatic patient. Further studies are needed to evaluate the safety of guselkumab in chronic HCV patients.

Background: Pregabalin is used in the treatment of neuropathic pain of various etiologies and as an adjuvant in epilepsy. Blockade of the α2δ subunit of L and N-type Ca-channels is its main mechanism of neurotropic action. Compared to other antiepileptics like phenytoin, valproate and lamotrigine, and other neuropathic pain medications such as amitriptyline and duloxetine, pregabalin has a relatively favorable safety profile and hence is a drug of choice for many geriatricians. Case Presentation: Here we describe a case of maculopapular rash induced by pregabalin in an older man, which resolved with withdrawal of the offending drug and conservative management. Conclusion: We have also conducted a literature review of similar cases and highlighted the clinical patterns and management strategies for pregabalin-induced skin rashes.