Current Drug Safety - Volume 18, Issue 2, 2023

The Coronavirus disease (COVID-19) outbreak is marked by infodemic amid conspiracy theories, false claims, rumors, and misleading narratives, which have had a significant impact on the global campaign against COVID-19. The drug repurposing provides a hope to curb the growing encumbrance of the disease but at the same time, it poses various challenges such as selfmedication using repurposed drugs and its associated harms. During the continuing pandemic, this perspective piece explores the potential hazards of self-medication and its attributing factors along with possible countermeasures.

Background: As a medical problem, hypertension is one of the most common disorders in cardiovascular disease. High blood pressure has been identified as one of the most familiar risk factors for the ongoing COVID-19 pandemic. We planned to explore the possible interactions between anti-hypertensive agents and drugs targeting SARS-CoV-2 with broad investigations of these medications' mechanism of action and adverse effects. Methods: Two co-authors searched the electronic databases (PubMed, Scopus, and Google Scholar) to collect papers relevant to the subject. The keywords searched were angiotensin-converting enzyme inhibitors (ACEI), angiotensin-II receptor blockers (ARBs), sympatholytic drugs (alpha-1 blockers, beta-blockers), vasodilators (calcium channel blockers, nitrates, and hydralazine), diuretics, chloroquine, hydroxychloroquine, lopinavir/ritonavir, remdesivir, favipiravir, interferons, azithromycin, anti-cytokine agents, glucocorticoids, anticoagulant agents, nitric oxide, and epoprostenol. Results: QT prolongation, arrhythmia, hypokalemia, hypertriglyceridemia are the most dangerous adverse effects in the patients on COVID-19 medications and anti-hypertensive drugs. Conclusion: This review emphasized the importance of the potential interaction between drugs used against COVID-19 and anti-hypertensive agents. Therefore, caution must be exercised when these medications are being used simultaneously.

There is a growing awareness of a disease at many levels, its treatment, and treatment outcomes including side effects. Alternative therapy techniques, herbal medicines and formulations are extensively acknowledged and practiced in India and around the world. Herbal medicine is usually considered being safe regardless of the absence of scientific evidence to support its claims. Several issues concerning the methods in which herbal medications are labelled, evaluated, sourced, and used are connected to herbal medicine. Herbal therapeutics in the management and treatment of diabetes, rheumatism, hepatic disorders and other mild to chronic diseases and disorders are widely accepted. However, the adversities are difficult to recognize. The idea that the nature is safe and may be taken without the prescription of a physician has resulted in widespread self-medication across the world, sometimes with disappointing results, side effects, or unpleasant after-effects. The existing pharmacovigilance paradigm and its accompanying tools were created in connection with synthetic medicines. Nevertheless, adopting these approaches to keep records of herbal medications’ safety poses a distinct challenge. This might be due to the variations in the usage of non-traditional medicines, which can offer unique toxicological issues whether taken alone or in conjunction with other medications. The goal of pharmacovigilance is to identify, analyse, explain, and minimize the adverse reactions and other drug-related complications associated with herbal, traditional, and complementary medications. Systematic pharmacovigilance is required to collect accurate data on the safety of herbal medications to create adequate guidelines for effective and safe usage.

Skin cancer is a life-threatening disease and has caused significant loss to human health across the globe. Its prevalence has been increasing every year and is one of the common malignancies in the case of organ transplant recipients, of which 95% constitute basal cell and squamous cell carcinomas. The prime factor causing skin cancer is UV radiation. Around the 20th century, sunlight was the primary cause of skin cancer. A novel hypothesis by US scientists stated that cutaneous melanoma was mainly due to recurrent exposure to the sun, whereas keratinocyte cancer occurred due to progressive accumulation of sun exposure. Management of skin cancer is done via various approaches, including cryotherapy, radiotherapy, and photodynamic therapy. Post-discovery of X-rays, radiotherapy has proven to treat skin cancers to some extent, but the indications are uncertain since it depends upon the type of tumour and surgical treatment required for the patient. Due to various limitations of skin cancer treatment and increased severity, there is a requirement for cost-effective, novel, and efficient treatment. Various nanocarriers such as SLNs, magnetic nanoparticles, gold nanoparticles, carbon nanotubes, etc., are the potential carriers in the management and prognosis of both non-melanoma and melanoma skin cancer. Various research and review databases and patent reports have been studied, and information compiled to extract the results. The review also discusses the role of various nanocarriers in treating and diagnosing skin cancer.

Objective: Interferon-alpha (IFN-α) is an important treatment modality for the hepatitis C virus (HCV). However, treatment with IFN-α is often associated with cognitive difficulties in HCV patients. Thus, this systematic review was performed to assess the effects of IFN-α on cognitive functioning in patients suffering from HCV. Methods: Relevant literature was identified by performing a comprehensive literature search in major databases including PubMed, clinicaltrials.gov, and Cochrane Central using a combination of suitable keywords. We retrieved studies that were published from the start of each database until August 2021. Results: Out of 210 articles, 73 studies were selected after removing the duplicates. In the first pass, 60 articles were excluded. Out of 13 full-text articles, only 5 articles qualified for qualitative analyses in the second pass. We observed conflicting results concerned with the use of IFN-α and the risk of neurocognitive impairment in HCV patients. Conclusion: In conclusion, we have observed conflicting results regarding the impact of INF-α treatment on the cognitive functioning of patients suffering from HCV. Thus, there is an urgent need for an extensive study to evaluate the exact association between INF-αtherapy and cognitive functioning in HCV patients.

Background: Per oral methadone maintenance therapy [MMT] was introduced as part of harm reduction strategy to manage rising numbers of HIV infections caused by intravenous use of illicit drugs. Method: We aim to review published articles related to the side effects of long-term methadone therapy, focusing on hematological derangements in human studies published between 1 January 2000 till 31 January 2021. Results: Our search databases include Web of Science, Scopus, and Medline. Our search yielded 971 articles, of which 55 articles were related to the effects of MMT on various organ systems: cardiovascular [n=12], respiratory [n=1], endocrine [n=10], central nervous system [n=12], neurobehavioral [n=10], gastrointestinal [n=1], and bone [n=1]. There were eight articles specifically related to the hematological side effects of chronic methadone therapy that include [i] immune system hyperactivation, [ii] reduced circulating lymphocytes, and [iii] increased blood viscosity. Conclusion: In view of all foreseeable health risks seen with prolonged methadone therapy, pharmacological modulation is warranted to find a better substitute for managing patients with opioid dependence.

Background: Cancer patients are more vulnerable to developing drug-drug interactions as multiple medications are administered concomitantly with cytotoxic agents to treat the underlying comorbidities. These drug-drug interactions often receive less medical attention and consequently are associated with adverse clinical outcomes. Objective: We intended to comprehensively characterize the drug-drug interactions among anticancer drugs and other concomitantly prescribed drugs in hospitalized lung cancer patients. Methods: A retrospective, observational, single-centre study was conducted on lung cancer inpatients from the medical records department of Kasturba Hospital, Manipal, India. Drug-drug interactions were identified using the drug interaction checkers of two drug information databases, Micromedex and Epocrates. These drug-drug interactions were categorized based on the source from which they were identified, mechanism, severity/significance, adverse consequences, and management strategies required. Results: Among 196 patients, 555 drug-drug interactions were identified in 185 patients using Micromedex and Epocrates. Based on the mechanism of action, 74% and 22% of the drug-drug interactions were classified as pharmacodynamic and pharmacokinetic respectively. 112 drug-drug interactions were recorded from Micromedex alone, while 549 interactions were found using Epocrates. The oral chemotherapeutic drug gefitinib was found to be associated with the highest number of drug-drug interactions. Conclusion: Drug-drug interactions were highly prevalent among hospitalized lung cancer patients. Structured screening and monitoring for these potentially clinically relevant drug-drug interactions by oncologists in collaboration with clinical pharmacists should be carried out prior to initiation and during anticancer treatment to prevent adverse clinical outcomes.

Background: Adverse drug reactions (ADRs) among pregnant women and pediatric patients are a significant public health concern. ADRs monitoring and documentation are considered essential practices to decrease the chances of ADRs and ensure the safe use of drugs. Objective: Therefore, the study was designed to evaluate the pattern of adverse drug reactions among pregnant women and pediatric patients in a tertiary care hospital. Methods: The study was conducted at Kalpana Chawla Government Medical College and Hospital, Karnal, Haryana, for a period of 2 years. During this period, ADRs reported by the healthcare professionals of gynecology and pediatric department to the ADRs monitoring centre of our institute were included in the study. Results: Out of 54 total ADRs, 40 ADRs occurred among pregnant women, and 14 ADRs were reported in pediatric patients. The majority of the ADRs were observed in the age group of 21-30 years (pregnant women) and 3-5 years (pediatric patients). Antibiotics were most commonly implicated in ADRs among pregnant women (60%) and pediatric patients (79%). In our study, the dermatological system was mostly affected among pregnant women and pediatric patients. Urticaria, contact dermatitis, and erythematous rash were the most commonly reported ADRs among pregnant women and pediatric patients. Conclusion: Over-prescribing and irrational use of antibiotics make these vulnerable populations more susceptible to ADRs and antibiotic resistance. Therefore, there is a need to create awareness among health care professionals regarding the spontaneous reporting of ADRs for ensuring drug safety and reducing morbidity and mortality among pregnant women and pediatric patients.

Background: The practice of disposing expired or unused medications by different households is generally not considered and is largely neglected. Objective: The study was carried out to determine the disposal practices regarding expired and unused medications in rural areas of Punjab, Pakistan. Methods: The study was conducted by interviewing different households and students (rural areas) from different universities in Punjab, Pakistan. The sample size was 676 and the questionnaire was used for data collection. Results: Out of 676 members, 552 (81.6%) had medications at the time of the visit. Only 14.5% (n= 80) were taking medication. Only 14.5% (n = 80) kept medication because the treatment was still in progress with the patients while 85.5% (n= 472) had medications that should be discarded. The main reasons for keeping the unused medications at home were completed treatment 34.7% (n= 164) after recovering from ailment. About 60.57% of female disposed the drugs in domestic trash while majority of male participants (48.72%) buried the drugs in the ground. Over 80% of respondents (n = 542) were unaware of the disposal methods. Almost half of the participants (n= 322) had no information about the impact of improper disposal. Statistically significant variations (p<0.001) were observed in the disposal practices depending on gender, age, education and occupation. Conclusion: Improper disposal of medication is a common practice in rural areas of Punjab, Pakistan. The launch of public education programs and the development of drug disposal facilities are very necessary to protect the environment and community health.

Background: Occurrence of adverse drug reactions (ADRs) in COVID-19 patients has not been extensively studied. Aim: The present study was conducted to analyze the pattern of suspected ADRs in the COVID-19 Intensive Care Unit (ICU). Methods: In this cross-sectional study, all the individual case study reports of patients admitted to the COVID ICU (August-October 2020) were analyzed for type of ADRs, system involved, suspected drug, onset time, time to revert and management. Results: Thirty six patients (out of 395 patients admitted) experienced 44 ADRs. Dermatological manifestations were the most frequent ADRs. Remdesivir was the most common drug associated with ADRs. The female gender, polypharmacy (>5 drugs) and presence of comorbidities were the independent risk factors for the occurrence of ADRs. Conclusion: Use of many of these drugs in COVID-19 is experimental and the literature does not guarantee their safety and efficacy. During these times of uncertainty, the results from the present study reinforce the importance of monitoring patients.

Background: Chronic infection with HCV is progressive worldwide health problem and the core reason for liver cirrhosis, portal hypertension, or hepatocellular carcinoma. HCV-G4 represents the most common threat to transplantation of the liver in Egypt. New interferon-free regimens have been started consuming direct-acting antiviral oral tablets for HCV cure. Objectives: In the current study, comparing the safety and efficacy of DAAs combination regimens including sofosbuvir with daclatasvir or sofosbuvir with simeprevir plus ribavirin for naïve cirrhotic Egyptian patients infected with HCV-G4 was our main goal. Methods: We recruited 150 naïve cirrhotic HCV patients from the Tropical patients’ clinic at Fayoum General Hospital. They were classified randomly into two groups, group one (n=75 patients) were administrated Sofosbuvir plus simeprevir (400 mg and 150 mg once daily respectively ) for twelve weeks, and group two (n=75 patients) were administrated Sofosbuvir plus Daclatasvir (400 mg and 60 mg once daily respectively) with ribavirin (1-1.2 gm daily weight-based) for twelve weeks. Clinical follow-up, laboratory investigations, and viral PCR were measured to detect treatment efficacy, safety, and any adverse events. Results: Sustained virological response rates (SVR12) were 92%and 90.7% in the first and second groups, respectively. The major unfavorable events were fatigue, arthralgia, and weight loss without statistically meaningful differences between study groups. However, anemia and headache were significantly widespread in the second group (P=0.0161 and 0.0495, respectively). We observed four patients with photosensitivity in group I and not observed in the second group. Conclusion: The current study revealed that DAAs are safe and effective in the cure of naïve cirrhotic patients chronically infected by HCV-G4 with better results in those treated with sofosbuvir plus simeprevir regimen.

Introduction: Drymaria cordata (Linn.) Willd is a creeping herb belonging to the Caryophyllaceae family, widely used as a traditional medicine in Africa and North-east India for various ailments. Many therapeutic applications of D. cordata have been reported in various scientific studies, but the teratogenicity study of this herb has not been documented till now. Methods: The present study aimed to assess the developmental toxic effect and median lethal concentration (LC50) of methanol extract of Drymaria cordata leaf (DCME) using zebrafish embryos. After spawning of male and female zebrafish, healthy zebrafish embryos were selected by microscopic screening and transferred into 96-well plate for the study. Embryos were exposed to DCME at concentrations ranging from 50-400 μg/ml in 2% DMSO from 24 hpf to 72 hpf. Results: Developmental and morphological abnormalities were microscopically evaluated. Fifty percent lethal concentration (LC50) of DCME was determined by observation from 24 hpf to 72 hpf. The concentration-dependent toxic effects of DCME on developing embryos of zebrafish were found in the study in a time-dependent manner. Conclusion: At 72 hpf, the median lethal concentration (LC50) of DCME was found with visible developmental defects, such as heartbeat rate, less pigmentation, oedema, spinal curvature, immature yolk sac as well as reduced hatching rate and a slow growth. The median lethal dose was found to be 448 μg/ml at 72 hpf for zebra fish embryos, meriting further studies on toxicological profiling of the plants.

Background: Self-medication has both negative and beneficial effects on people's health, as the COVID-19 epidemic has demonstrated. The goal of the study is to look into the epidemiology of self-medicated medications used for respiratory symptoms, as a COVID-19 preventive, for its symptoms, or after a positive COVID-19 test, and to see how symptom relief is viewed in India, as well as what demographic factors encourage self-medication. Methods: Using a trial version of Qualtrics Core XM software to prototype 24 surveys, a webbased questionnaire was built, tested, and disseminated in several Indian states. Result: In the survey, 519 candidates participated. 43% of respondents reported that all symptoms were relieved. However, just 39% of all respondents took the government-recommended Ayushkwath, and 56% took a vitamin C tablet to improve immunity. Aspirin, ibuprofen, and azithromycin were shown to be the most commonly used medications for various symptoms, including fever, weariness, cough, sneezing, loose motion, and immune boost, and breathing problems. Conclusion: Self-medication was common, with many people taking drugs for which there was little scientific evidence. The frequency of self-medication was connected to age, region, and employment position.

Background: The practice of self-medication appears to be much more rampant during the- COVID-19 pandemic. Hence, awareness about its consequences is essential among the general population during the current circumstances. Objectives: To study the prevalence of and perception towards self-medication, as well as its determinants among the general population of Mangalore. Methods: This cross-sectional study was done during the second wave of the COVID-19 pandemic in August 2021. Data were collected using a Microsoft form disseminated among residents of Mangalore through WhatsApp and email. Results: The mean age of the 225 participants in this study was 34.5±15.2 years. Self-medication practice was indulged by 77(34.2%) out of the total participants. The most common symptom for which self-medication was practiced was for common cold [54(70.1%)], and the most commonly used drug was paracetamol [67(87%)]. 167(74.2%) participants felt that self-medication practices were harmful, but the rest 58(25.8%) felt that it was not a harmful practice. 116 (51.6%) participants felt that the advertisements in mass media and social media promoted self-medication practices among people. Out of the 69(30.7%) participants who felt that self-medication practice was acceptable during the current circumstances, the majority [66(95.6%)] felt that it was better to avoid visiting any doctor or health care facility presently to avoid acquiring COVID-19. In the multivariable analysis, participants with a history of self-medication among their family members, relatives, or friends were more likely to indulge in self-medication (p<0.001). Perceptions that self-medication practices were harmful were more among females (p=0.0397). Conclusion: More than one-third of the participants indulged in self-medication practice. More than one-fourth of the participants felt that self-medication practices were not harmful. About one-third felt it was acceptable, and most of them felt so to avoid the risk of contracting the Coronavirus infection. Awareness of its hazards, particularly among males and those with a family history of selfmedications, is required at Mangalore.

Background: Despite being the oldest therapy for heart failure, the use of digoxin is still controversial due to the narrow margin of safety. In Indonesia, digoxin is still considered one of the treatments for heart failure. However, analysis of intoxication has never been reported. This study aims to analyze the occurrence of digoxin intoxication, rate of rehospitalization and one-year survival in heart failure patients under digoxin treatment. Methods: A cross section-observational study was conducted at Harapan Kita National Cardiovascular Centre from January 2017 to December 2018 on heart failure patients who received digoxin therapy and had data on serum digoxin level. Intoxication was defined as the presence of specific ECG alteration(s), at least one extra-cardiac symptom(s) and further classified as definite (serum digoxin >2 ng/mL), probable (serum digoxin 0.91-1.99 ng/mL), or possible (serum digoxin 0.5-0.9 ng/mL). Risk factors of intoxication were analyzed by Chi-square test, and one-year survival was analyzed with Kaplan Meyer method. Results: 54 of 195 patients (27.69%) were classified as having intoxication, consisting of 32 (16.41%) definite, 19 (9.74%) probable, and 3 (1.54%) possible. Renal insufficiency was revealed as a significant influencing factor of digoxin intoxication with RR 2.48 (CI 1.13-5.464, p=0.016). Overall one-year survival of patients receiving digoxin was 259 days in the intoxication group and 307 days in the non-intoxication group. One-year rehospitalization was 11.8% in patients who received digoxin and 29.2% in those without digoxin (p=0.085). Conclusion: The proportion of digoxin intoxication in heart failure patients was 27.69%. Renal insufficiency was revealed as a significant influencing factor of intoxication. There was a tendency of reduced hospitalization in those who received digoxin.

Background: Adverse drug events (ADE) and medication errors (ME) provide large numbers of victims. Older people are more susceptible to these events, due to the continuing search for several chronic degenerative disease treatments. The Third Global Patient Safety Challenge announced the objective of reducing unnecessary polypharmacy, encouraging deprescription, and aiming to ensure the prescription of medications in an appropriate manner, based on the best evidence and taking into account the individual factors of people. Objective: To evaluate whether Pharmaceutical Care (PC), when inserted in a geriatric ward and the context of person-centered health care, cooperates with the safety of pharmacotherapy in older individuals in Brazil. Methods: This is an investigative, single-arm, preliminary study. Inclusion criteria: individuals aged ≥60 years and admitted to the geriatric ward between August 2019 to January 2020. The PC (with the practice of pharmacotherapeutic follow-up, medication reconciliation, and pharmacotherapy review) was made available to identify ADE and ME, as well as the associated factors and clinical outcomes, were analyzed. Results: 60 participants were included. It was found that, on hospital admission, 93.3% of them were polymedicated and 86.7% had a history of using potentially inappropriate medications (PIM). ADE and ME were detected in 43 individuals (71.7%) and, in total, 115 incidents were identified, with drugs that act on the nervous system associated with them (31.9%). Acceptance of the PC's recommendations reached the rate of 85.2%. Polypharmacy (p=0.03) and the presence of multiple diseases (p=0.03) had an effect on the presentation of ADE and ME. The number of medications in use decreased in the comparison between admission and hospital discharge (p<0.0001). Conclusion: This investigative study indicated that ADE and ME are linked to the polypharmacy in use at the beginning of hospitalization. On the other hand, we showed that the PC (inserted in the multidisciplinary team) contributed to the deprescribing of medications at hospital discharge. Therefore, the PC can provide improvements in this scenario.

Introduction: Liposomal amphotericin B is a widely used broad-spectrum antifungal drug. It was developed to reduce nephrotoxicity and maximize the therapeutic utility of amphotericin B in the treatment of invasive fungal infections. Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity syndrome commonly associated with aromatic antiepileptic drugs. Liposomal amphotericin-B was associated with DRESS syndrome in only one case. Case Report: We report an exceptional case of possible DRESS syndrome associated with liposomal amphotericin B in a 31-year-old male renal transplant recipient. Seventeen days after starting liposomal amphotericin B for visceral leishmaniosis, he developed a skin rash with elevated liver tests. Liposomal amphotericin B was then discontinued. A favourable outcome was slowly observed in one month. Results and Conclusion: This case scored two (possible case) based on the criteria adopted by the European group RegiSCAR. The Naranjo score for liposomal amphotericin B was four (possible).

Background: Acenocoumarol is an anticoagulant with numerous drug reactions. We report here, an unusual interaction between acenocoumarol and azathioprine. Case Presentation: A 35-year-old woman, treated with acenocoumarol for thrombosis of the superior mesenteric vein, was prescribed azathioprine for Crohn’s disease. Three days later, INR values decreased from 2.36 to 1.48. The dose of acenocoumarol had to almost be doubled to reach an INR value of 2.56. The interaction between azathioprine and acenocoumarol was then suspected. Few similar cases of interactions between azathioprine and another coumarin derivative, warfarin, have been reported. To our knowledge, this is the second case of such interaction reported with acenocoumarol in literature. Conclusion: Thus, despite the rarity of this interaction reporting, we draw attention to the importance of close monitoring of INR values in patients treated with acenocoumarol associated with azathioprine.

Introduction: Although rare, some patients may have a vitamin B12 allergy. Crohn’s disease commonly leads to significant vitamin B12 deficiency, especially in those patients that have undergone ileal resection. In these difficult cases, vitamin B12 desensitization may be required. Case Presentation: Here, we report a successful case of a serial outpatient subcutaneous vitamin B12 desensitization protocol in a 35-year-old female with a past medical history of Crohn’s disease status post ileal resection, subsequent vitamin B12 deficiency, and allergy to subcutaneous vitamin B12. Conclusion: This is the first subcutaneous vitamin B12 desensitization protocol reported to have been safely performed in the outpatient setting.