Current Drug Safety - Volume 15, Issue 3, 2020

Pharmaceuticals are beneficial to humankind and emerged as crucial arms to treat/manage multiple disease pathogenesis in the present era. In analogous, these medicines/ medical devices should be used cautiously as they possess a potential threat to induce multiple undesired effects that may be related to human health or the environment. Daunting effects may arise due to the improper disposal of unused/expired medicines. Hence, to minimize such harm, there should be adequate knowledge and practice among the population regarding the safe disposal of unused/expired medicines or related pharmaceutical devices. The lack of approved information regarding safe disposal of such substances may invite serious concerns like environmental pollution, which may induce immediate health hazards to the present population and upcoming future generations. There are numerous ways to dispose of, or manage the unused and expired pharmaceutical substances. Sharing the medicines among siblings, friends, and family members are never free from serious health risks. Storing the unused and expired medicines in the home increases the risk of intentional or accidental ingestion of such substances and may create a health emergency. Disposing medicines like household and municipal waste may lead to environmental pollution and harm to humans and animals. The present review finds the multiple unsafe ways of disposal of unutilized medications/tools. Furthermore, it also summarizes the disposal pattern of unutilized medications among the few developed and undeveloped nations.

Purpose: The purpose of this quantitative comparative study was to examine the possible relationship between nicotine replacement therapy (NRT) and cardiac disorder risk by comparing the rates of cardiac disorder risk of NRT with cardiac disorder risk of non-replacement drugs among smokers seeking smoking cessation. Methods: The study used retrospective quantitative design, which involved the collection of secondary data from the adverse event reporting system (FAERS) database of the U.S Food and Drug Administration (FDA). Rates of cardiac disorder were compared between the NRT group and non- NRT (varenicline and bupropion) group. Statistical analyses involved using a 2x2 contingency table and logistic regression to calculate odds ratio (reporting odds ratio (ROR)). Results and Discussion: Unadjusted ROR was 0.45 (95% confidence interval [CI] 0.28, 0.70). With age and sex as confounding factors, the smokers in the NRT group still had lower odds of having cardiac disorder risk than the non-NRT group (adjusted ROR=0.44, 95% CI 0.28, 0.70). Conclusion: Our study findings showed lower cardiac disorder risk with the NRT group compared to the non-NRT (varenicline and bupropion) group. While the study did not aim to undermine either using NRT or non-NRT for smoking cessation therapy to prevent smoking illness, the study results offer informed findings that could potentially improve current smoking cessation management using NRT intervention among smokers and enhance smokers’ health outcome. Despite the negative signal detection of cardiac disorder risk with NRT as compared to non-NRT in final findings, we still recommend further research on the causal relationship between NRT and non-NRT and cardiac disorder risk.

Background: While off-label drug use is common and sometimes necessary, it also presents considerable risks. Therefore, measures intended to prevent or reduce the potential exposure to off-label risks have been recommended. However, little is known about community pharmacists’ beliefs regarding these measures in Malaysia. Objectives: This study examined community pharmacists’ beliefs towards risk minimization measures in off-label drug use in Malaysia and assessed the relationship between perceived risk of off-label drug use and beliefs towards risk minimization measures. Methods: A cross-sectional survey was conducted among 154 pharmacists practicing in randomly selected community pharmacies in Kuala Lumpur and the State of Selangor, Malaysia. Results: The majority agreed or strongly agreed that adverse drug events from the off-label drug should be reported to the regulatory authority (90.9%) and the off-label drug should only be used when the benefit outweighs potential risks (88.3%). Less than half (48.1%) agreed or strongly agreed that written informed consent should be obtained before dispensing off-label drugs and a majority (63.7%) agreed or strongly agreed that the informed consent process will be burdensome to healthcare professionals. Beliefs towards risk minimization measures were significantly associated with perceived risk of off-label drug use regarding efficacy (p = 0. 033), safety (p = 0.001), adverse drug rection (p = 0.001) and medication errors (p = 0.002). Conclusion: The community pharmacists have positive beliefs towards most of the risk minimization measures. However, beliefs towards written informed consent requirements are not encouraging. Enhancing risk perception may help influence positive beliefs towards risk minimization measures.

Background & Aims: The objective is to ascertain the pattern of potential drug-drug interactions (pDDIs) and record any observed DDIs and adverse events (AEs) in hospitalized Beninese cardiology patients from Sub-Saharan Africa and analyze all risk factors associated with DDIs and AEs. Methods: It was a prospective study in which data including AEs were assessed from medical files and interview of patients and their relatives. Patients who were treated with more than two drugs and who remained in the hospital for at least 48 hours were included. A computerized database system Pharma IAM- VIDAL version 2011 was used to identify the pattern for potential DDIs. Results: 156 patients were included in this study. The prevalence of potential DDIs was estimated at 93 % (145/156). Forty (5.1%) among 804 potential DDIs identified were observed clinically. The observed DDIs were attributable to low blood pressure (27.5%), hyponatremia (22.5%), hemorrhage (20.0%), hyperkalemia (17.5%) and nephrotoxicity (7.5%). The combination of spironolactone and furosemide resulted in hyponatremia while the combination of enoxaparin and potassium resulted in hyperkalemia. ACE inhibitor (or ARAII) in combination with furosemide resulted in the nephrotoxicity cases observed. Enoxaparin, Acetyl salicylic acid, Acenocoumarol and Clopidogrel were decreasingly involved in the pairs of drugs responsible for observed hemorrhages. 29 patients out of 156 (18.6%) had at least one AE. AEs were mainly (34.2%) of metabolic type. Severe AEs, which represented 18.4% was mostly from nephrotoxicity and metabolic disorders. More than 14 active substances multiplied the risk factor for AEs occurrence by 42, while more than 14 days hospitalization increased this risk by 42. Conclusion: This study highlights the need to optimize treatments by strictly regulating blood pressure, serum sodium and potassium levels, coagulation parameters and looking for clinical signs of hemorrhage. Physician should be aware of certain drug associations that may carry a risk of severe adverse events.

Background: Incidence of Antitubercular Therapy (ATT)-induced hepatotoxicity is higher in India when compared to Western countries. As the occurrence of ATT-induced hepatotoxicity is unpredictable, serial intensive monitoring of hepatic function is now being recommended by the American Thoracic Society in individuals at high risk. This study was done to evaluate the risk factors for the development of ATT induced hepatotoxicity in India. Methodology: In this prospective, observational study, patient characteristics of microbiologically/ radiologically/ histopathologically confirmed tuberculosis were prospectively compiled. Serial liver function tests were done once a month in all patients. Patients who developed ATT-induced hepatotoxicity were considered as the study group and those who did not develop the event as a control group. The primary outcome measure was to estimate the hazard ratios associated with risk factors for the development of ATT induced hepatotoxicity. Cox Regression Analysis was done using SPSS 20. Results: A total of 200 patients were enrolled in the study, of them, 14% developed ATT-induced hepatotoxicity and 86% did not develop the event. The baseline liver function tests in the study group and control group were within normal limits. Female gender, alcoholism, HIV co-infection and age >35 yrs were identified to have a higher risk for development of ATT-induced hepatotoxicity, while cases with pulmonary tuberculosis were found to be at lower risk of developing event. Conclusion: Intensive liver function monitoring needs to be done in patients with these risk factors, female gender, alcoholism, HIV co-infection, extra-pulmonary tuberculosis and age >35 yrs.

Background: Prenatal antiepileptic drug exposure could demonstrate both congenital malformations and behavioral impairments in offspring. Objective: This study was performed to assess the effects of prenatal exposure to pregabalin (PGB) on pain response, anxiety, motor activity and some behavior of adult offspring rats. Methods: Pregnant Wistar rats received PGB (7.5, 15 and 30 mg/kg/ip) during embryonic days 9.5- 15.5. The pain response, anxiety-like behaviors, locomotor activity, motor balance and coordination and anhedonia of adult offspring were examined by tail-flick and hot plate test, open field test, elevated plus maze (EPM), beam balance test and sucrose preference test in their 60th day of life, respectively. Results: Prenatal exposure to PGB revealed significant dose-dependent reduction in pain sensitivity (increase in pain latency response) in the hot plate test, especially in females, while anxiety-like behavior assessed in EPM and open field significantly reduced in males. In the open field, locomotor activity reduced significantly after exposure to PGB 30 mg/kg and motor coordination decreased dose-dependently, especially in males. Anhedonia, as an indication of sucrose preference or pleasure response, was not changed. Conclusion: These findings suggest that prenatal PGB exposure could be associated with significant changes in pain response, anxiety, locomotor activity and coordination in adult offspring rats.

Background and Objective: Adverse drug reactions (ADRs) are associated with increased economic burden on the society. Monitoring of ADRs can help in decreasing the incidence of preventable adverse reactions. Methods: Under Pharmacovigilance Program of India, collection and reporting of ADRs has been going on at Dayanand Medical College and Hospital since January 2011. Here, we have analyzed the individual case safety reports (ICSRs) reported and uploaded between January 2017 and June 2019 from our centre. The ADR form provided by PvPI was used for collecting information, and the causality assessment was done according to the WHO-UMC scale. Results: A total of 498 ICSRs were uploaded through Vigiflow software during this period. Highest number of ADRs were recorded in the age group of 31-45 years (29.01%) and the least number of ADRs were recorded in the children less than 15 years of age (6.76%). General Medicine ward reported the highest number of ADRs and the antibiotics were most commonly associated with ADRs (26.21%), followed by antipsychotics (13.83%) and NSAIDs (12.14%). More than 90% of ADRs were non-serious (93.17%) and most of the ADRs were skin and soft tissue related (49.20%). Conclusion: Spontaneous reporting among indoor patients shows highest number of ADRs with use of antibiotics and almost all of the ADRs were non-serious in nature. Almost half of the total ADRs were skin and subcutaneous tissue related. Continuous efforts are required for further strengthening of the pharmacovigilance program of India.

Rationale: Linezolid (LNZ) induced Cutaneous Adverse Drug Reactions (CADRs) have rare atypical presentation. Till date, there are very few published case reports on LNZ induced CADRs among the multidrug-resistant patients suffering from Infective Endocarditis (MDR IE). Here, we present a rare case report of LNZ induced CARs in a MDR IE patient. Case Report: A 24-year-old female patient was admitted to the hospital with chief complaints of fever (101°C) associated with rigors, chills, and shortness of breath (grade IV) for the past 4 days. She was diagnosed with MDR IE, having a prior history of rheumatic heart disease. She was prescribed LNZ 600mg IV BD for MDR IE, against Staphylococcus coagulase-negative. The patient experienced flares of cutaneous reactions with multiple hyper-pigmented maculopapular lesions all over the body after one week of LNZ therapy. Upon causality assessment, she was found to be suffering from LNZ induced CADRs. LNZ dose was tapered gradually and discontinued. The patient was prescribed corticosteroids along with other supportive care. Her reactions completely subsided and infection got controlled following 1 month of therapy. Conclusion: Healthcare professionals should be vigilant for rare CADRs, while monitoring the patients on LNZ therapy especially in MDR patients as they are exposed to multiple drugs. Moreover, strengthened spontaneous reporting is required for better quantification.

Dabigatran etexilate, a direct thrombin inhibitor, was recently introduced in clinical use to prevent thromboembolic events in patients with risk factors (such as non-valvular atrial fibrillation or deep vein thrombosis). Dabigatran is not recommended in patients with creatinine clearance below 30 mL/min. More than 85% of the drug is eliminated by the renal route while the remaining part via the enteral route. Acute renal failure can result in an unexpected increase in serum levels of Dabigatran. In elderly, renal dysfunction, co-morbidity, and concomitant intake of different drugs could make the dosage of Dabigatran challenging. We present a case of an elderly man who suffered a severe accidental dabigatran intoxication with acute liver toxicity recovered after dialytic treatment and Idarucizumab.

Background: Vinblastine (VBL) is a cytostatic drug frequently applied in children with lymphoma and progressive low-grade glioma (LGG), with hematotoxicity as the main side effect. Case Report: Here, the case of a 7-month-old girl with tumor progression of an LGG during standard chemotherapy with carboplatin and vincristine, is presented. Switching to VBL led to a 20-30- fold increase of transaminases (grade IV CTCAE 5.0), spontaneously resolving after the end of treatment. The toxicity is possibly age-related since it did not re-occur at the restart of VBL at 4 years old. This finding might have consequences for toxicity screening in future protocols, especially when including infants.

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction characterized by the development of numerous sterile and non-follicular pustules on an erythematous base with no or minimal mucous membrane involvement associated with fever and leucocytosis. Cefixime is a cephalosporin-type beta-lactam antibiotic commonly used for the management of several infections. The Cefixime-induced AGEP cases are known to be rare. Here, we present the case report of a 26-year old female who developed Cefixime-induced AGEP with mucosal membrane involvement. To the best of our knowledge, this is the first case to report the mucosal membrane involvement in Cefixime-induced AGEP. We are presenting this case report to draw the attention on the existence and plethora of symptoms of Cefixime-induced AGEP hoping that the clinicians will reckon these in their differential diagnosis and implement the appropriate management strategies for this rare adverse event in their clinical practice.