Current Drug Safety - Volume 15, Issue 1, 2020

Introduction: Several drugs were withdrawn from the market due to safety. Objective: The aim of this study was to describe data supporting drug withdrawal from the market due to safety reasons in countries belonging to the World Health Organization. Methods: We analyzed drugs withdrawn from the market between 1990 and 2010. All medicine agencies of the countries belonging to the Program for International Drug Monitoring of the World Health Organization were contacted. To complete data, Medline, reference books and available drug databases were also searched. Information sources on which authorities based their withdrawal were categorized and the average time between the first date of exposure and withdrawal was calculated and stratified. Results: A total of 133 drugs that met the inclusion/exclusion criteria were withdrawn from the market due to safety reasons in the period reviewed (1990 - 2010). Hepatotoxicity (n=36, 27.1%), cardiac disorders (n=25, 18.8%), hypersensitivity (n=17, 12.8%) and nephrotoxicity (n=14, 9.8%) were the major reasons responsible for 69.2% of all drugs withdrawn. In most cases, Information Sources for drug withdrawal were spontaneous reports and/or case reports (n=86, 64.7%), followed by clinical trials (n=24, 18.0%). The average time between the introduction of a drug and its withdrawal due to safety reasons was 20.3 years (SD±13.8). Conclusion: According to available and published evidence, there is no gold standard to identify risks associated with drug exposure. These findings strengthen the role of different information sources within the drug safety review process.

Background: Stocking unused or expired medicines or donating these to others can lead to accidental or inappropriate ingestion, increasing the risk of adverse drug reaction(s) and even lead to antibiotic resistance. Further improper disposal of expired or unused medicines is associated with environmental pollution, health hazards and damage to ecosystem. Ecopharmacovigilance is an important area in this context. Objective: To explore the awareness and disposal practices of unused/expired in the general public. Materials and Methods: The current study is an observational, cross-sectional, questionnaire-based study conducted in 956 medicine consumers in New Delhi and National Capital Region, India. The knowledge, attitude, and practice of consumers regarding the disposal of unused medicines were evaluated. Results: The majority (89.9%) of consumers opined that expiry of medicine(s) meant for completion of shelf life, production of toxic chemical and loss of or decreasing of beneficial effects of medicines. Majority (87%) of the consumers stored medicines at home. Almost all (92.6%) of the consumers threw away the expired medicines after storing for few days. Consumers discarded the expired medicines mainly in household trash (73%). The majority (93%) of consumers were in favour of a government program to collect unused or expired medicines from their home. Conclusion: The knowledge and practices of consumers towards disposal of unused and expired medicines needs to be improved. Health care professionals, government and policy makers should offer training to educate and guide the general public on safe and proper disposal practices of expired or unused medicines.

Background and Aims: Sedation and analgesia are important elements of endoscopic examinations; sedation for colonoscopy aims to relieve patient discomfort and anxiety, improve the outcome of the examination, diminish the patient’s memory of the event and achieve comfortable and technically successful endoscopic procedure. Methods: Our prospective study was carried out on 150 patients who were referred for colonoscopy; they were divided into two groups based on the pre-endoscopic sedation given for them: propofol fentanyl or propofol ketamine. Detailed histories, thorough physical examinations, and routine laboratory investigations were performed for all patients, along with monitoring of their vital signs and oxygen saturation levels (before, during and after colonoscopy), to assess safety, efficacy, recovery times, complications of the sedative drugs, comfort of the patients and endoscopists. Results: There was no statistically significant difference between the two groups in terms of age, sex and Body Mass Indexes (BMI). With respect to their Mean Arterial Blood Pressures (MAPs) and heart rates, there was high hemodynamic stability in the propofol ketamine group, and both the groups were efficacious, although the propofol fentanyl group had shorter recovery times than the propofol ketamine group (3±1.7 minutes and 4±2.8 minutes, respectively). However, nausea, vomiting and hypoxia were common in the propofol fentanyl group, while hallucinations were common in the propofol ketamine group. In propofol fentanyl group; there was a significant decrease in the heart rate more common in females (with age range 39-58 years) during and after colonoscopy [p value 0.01]. Conclusion: Sedation with propofol ketamine during colonoscopy was found to be safe and efficacious to achieve hemodynamic stability with fewer complications than propofol fentanyl.

Background: Topical corticosteroids are highly effective compounds that are now widely used in dermatology for the treatment of various autoimmune and inflammatory disorders. Many corticosteroids are misused for diverse indications such as pigmentation, acne, pruritus, fungal or bacterial infections, rashes, and numerous other conditions. These products contain various constituents, most of which have hazards or toxic elements. Objective: The aim is to raise awareness among individuals in the city of Basrah, Iraq about the uses and abuses of applying fake products to the face to inform the consumers about potential harmful adverse effects. Methods: This study was a prospective multi-center clinic questionnaire of a demographic that involved the outpatient dermatology departments at the Al-Basrah teaching hospital and the Abu Al-Khaseeb hospital as well as the private clinics of two dermatology specialists in Basrah. A total of 235 patients with facial dermatoses secondary to the application of topical corticosteroids and counterfeit products or, a mixed formulation, for cosmetic purposes were recruited. Results: Most enrolled patients were female with 10-20 years aged group. The majority applied these products due to friends or pharmacy encouragement. Motivations for the use of these products included: skin fairness, lightening, and general cosmetic. Interestingly, acne and erythema were common whilst, atrophy, dryness, telangiectasia, and hirsutism appear on long- term use only. Conclusion: The abuse of counterfeit cosmetic products and topical corticosteroids is in progress and they have adverse health events. There are many causes behind the abuse but the lack of education, lack of restriction, profitable for sellers and low prices are the main.

Background: Pharmacists play an essential role in educating the epileptic patients about their disease and their medications. Improving the patient’s awareness may lead to improve their compliance and decrease drug-drug interaction and ultimately improve their quality of life. Objective: This study aimed to assess the pharmacist’s knowledge about anti-epileptic drugs in Khartoum State, Sudan. Methods: We conducted a descriptive cross-sectional study in Khartoum State, Sudan. Proportionate stratified sampling was used to determine the targeted Pharmacies, and all pharmacists who were present in the selected pharmacy at the time of data collection and fulfilled our selection criteria were included in the study. A structure closed-ended questionnaire was used to collect quantitative data from candidates. Results: Majority of participants were female (66.9%), less than 30 years old (66.7%) and have less than 5 years of experience (62.1%). Unfortunately, the majority of the participants (85.3%) had poor knowledge, and only (14.7%) of them had good knowledge. Furthermore, the study revealed that age (p =.030), years of experience (p =.026) and the degree in pharmacy (p = .003) were significantly associated with knowledge level. Conclusion: Majority of the pharmacists in Khartoum State have poor knowledge about anti-epileptic drugs. Further research is needed to investigate the actual factors behind this knowledge gap and to propose interventions to improve the pharmacist’s knowledge and practice aiming to improve the quality of health care provided to the patients.

Introduction: Oral anticoagulants, including vitamin K inhibitors (VKAs) and direct anticoagulants (DOACs) are important for preventing and treating thromboembolic diseases. However, they are not recommended for use in all patients due to negative side effects and adverse drug reactions (ADRs). Currently, there is a paucity of information about their use in real life. Therefore, the aim of this pilot study is to report on the rate of serious ADRs in oral anticoagulant users, determine patient characteristics associated with increased risk of ADRs, and identify possible management strategies for reducing risk of ADRs within a hospital setting. Methods: Patients admitted to the Internal Medicine Department of the Vimercate Hospital were recruited between November 1, 2015 and October 31, 2016. All patients reporting an ADR associated with anticoagulant use were selected. Demographic, clinical, and observational data were extracted from electronic hospital records, in particular, by the hospital discharge letters and other clinical records. The main outcome of the study was to evaluate the incidence of anticoagulants serious adverse drug reactions conditioning hospital admission, the percentage of preventable reactions, and the determinants of those. Results and Discussion: Of the 2,064 admissions, 102 (4.9%) eligible patients were identified. Age ranged from 60-95 years (mean = 81.9, standard deviation = 6,59) and 47.1% (n=48) were female. Of the 102 cases, 68 used VKAs and 34 used DOACs. The most common admission diagnosis was heart failure following anemia or hemorrhage (56 cases), followed by acute hemorrhage (with or without anemia; 29 cases), and anemia not associated with evident hemorrhage (17cases). The majority of VKA users (n=65, 95.6%) had a high risk of major bleeding. ADRs were found to be preventable in 96% of VKA users and 68% of DOACs users. Conclusion: This study highlights the large percentage of ADRs from oral anticoagulants that can be avoided with more careful patient management. Periodic check-up of cardiac and renal function, as well as blood count, may be useful for reducing the risk of ADRs, especially in older DOACs users. Further research is needed to get new data to improve the patients monitoring system.

Background: Self-medication could be risky behavior and has negative effects. While Over the Counter (OTC) drugs are available at drugstores, the behavior has become prevalent among the general population. Objective: This study aimed at surveying self-medication behavior among medical sciences students of Shiraz, Iran. Methods: A sample of 396 students from medical, paramedical, and health sciences disciplines were included in this cross-sectional study. They were asked to fill a questionnaire about their demographics and socioeconomic status, medication usage and self-medication in the last six months, information about the correct use of medication, and information about negative results of selfmedication. Data were analyzed using chi-square, t-test and logistic regression model using R statistical software. Results: Almost 72% of participants reported self-medication in the past sixth months. The main reasons included trust in their own diagnosis (59.9%), mildness of the disease (56.6%), and having previous experience about the disease (56%). Cough or cold (84.5%), headache (66.3%), and body pain (60.2%) were the most frequent diseases that led to self-medication. The majority of the participants (77.7%) reported they select their medicine on their own decision. Furthermore, self-medication was highly related to having medicine stock at home (OR=2.692), having less information about negative results of self-medication (OR=0.835), and more non-syllabus study time (OR=1.041). Conclusion: Although, medical science students have information about the treatment of illnesses, they should be more informed about negative results and side-effects of self-medication. They should also share their knowledge with society to decrease self-medication.

Background: Chronic Hepatitis C (CHC) is a common progressive healthcare challenge that leads to liver cirrhosis, liver failure, and hepatocellular carcinoma. The optimum therapy was a combination of pegylated interferon and ribavirin, which was associated with moderate response and severe side effects. Sofosbuvir revolutionized CHC treatment, especially in combination with other antiviral agents. Objective: The aim of this study was to compare and evaluate the safety and efficacy of sofosbuvir/ daclatasvir versus sofosbuvir/ledipasvir for the treatment of non-cirrhotic naïve patients with chronic Hepatitis C Virus (HCV) genotype 4 infection for 12 weeks. Methods: One hundred CHC genotype 4 patients (70 females, 30 males) were recruited from the hepatology clinic at the Beni-Suef general hospital. Patients were randomly allocated into two groups that received a 12 weeks treatment of either sofosbuvir 400 mg/daclatasvir 60 mg or sofosbuvir 400 mg/ledipasvir 90 mg. The sustained virological response 12 weeks post-treatment (SVR12) (HCV RNA < Lower Limit of Quantification (LLOQ)) was determined to evaluate efficacy. The clinical laboratory tests and any reported adverse effects starting from the administration of the first dose till 30 days after the last dose were assessed to evaluate safety. The main outcome measure was the assessment of the safety, efficacy and compliance of sofosbuvir/ daclatasvir versus sofosbuvir/ledipasvir for the treatment of non-cirrhotic naïve CHC genotype 4 patients for 12 weeks. Results: SVR12 was achieved by 98% and 96% of patients receiving sofosbuvir plus ledipasvir and sofosbuvir plus daclatasvir, respectively. The most common adverse events reported were headache, and fatigue. No patients discontinued treatment due to adverse events. Conclusion: The findings from this study suggest that the 12 weeks treatment regimens of sofosbuvir plus daclatasvir and sofosbuvir plus ledipasvir were both efficacious and well-tolerated in patients with HCV genotype 4 infection. Impact on Practice: In this paper, we report on the most recent approaches in the treatment of Hepatitis C genotype 4 patients in Egypt. This is significant because this article focuses on comparing the efficacy and tolerability of the most commonly used antiviral drugs in Egypt.

Introduction: Levofloxacin is a fluoroquinolone active against both gram-negative and gram-positive bacteria with a well-defined margin of safety and efficacy. It has various labeled adverse effects like other fluoroquinolones but its adverse effect like desquamation is rarely reported. Methods: We present a case report of levofloxacin-induced desquamation in an Indian patient. Case Report: A-38-year old female patient presented to the outpatient department, with chief complaints of peeling off her epidermal skin. Initially, Desquamation started on her greater finger, which slowly spread to her hand, feet, lower limbs as well as upper limb and neck region. She was prescribed Levofloxacin for respiratory tract infection. Results and Discussion: Considering temporal relationship, upon causality assessment, (Adverse Drug Reaction) ADR was found to be likely, moderate and probable. The drug was withdrawn along with the initiation of supportive therapy and reaction subsided. Conclusion: Although adverse drug reactions like desquamation are not fatal, this induces anxiety in the patients and reduces patient’s quality of life. This case report will help keep physicians vigilant about the current adverse drug reaction, helping in the early detection and management of ADR.

Background: Olmesartan, an antihypertensive drug, may be associated with a severe “sprue-like enteropathy”. Objectives: To report a case of Olmesartan enteropathy demonstrated by video capsule endoscopy distally from the second duodenum along with the whole small bowel before and after drug withdrawal. Case Presentation: A 81-years-old man was referred for asthenia, chronic watery diarrhea and anasarca (ascites, pleural effusion and edemas of superior and inferior limb). The only comorbidity was hypertension treated with Olmesartan. All causes of infective and inflammatory chronic diarrhea were investigated and excluded. Upper endoscopy was normal; histological examination of the second portion of the duodenum showed moderate and patchy infiltration of lymphocytes at mucosal and intra-epithelial level with intermittent partial villous atrophy. The possibility of adverse drug reaction, estimated by Naranjo scale, showed a score of 7, indicating a strong probability. Olmesartan was then withdrawn. However, because of severe clinical general condition, we preferred to corroborate our diagnostic work-up by a non-invasive investigation, i.e. video capsule endoscopy, which showed jejunal and ileal mucosal alterations (mosaic pattern, diffuse hyperemia, severe edema, consequent apparent reduced lumen, diffuse thickening of intestinal folds, multiple erosions, patchy lymphangectasia). After 14 days, the resolution of anasarcatic state and hydroelectrolytic imbalances was observed. Nine months later, small-bowel video-capsule demonstrated mild mucosal hyperaemia and mosaic pattern. Conclusion: Our case could give new insights in the field of Olmesartan associated enteropathy by highlighting the possibility of distally main lesion location and, therefore, the usefulness of video capsule endoscopy in the presence of doubtful diagnostic features.

Background: Psoriasis is a cutaneous inflammatory condition characterized by an altered turnover of keratinocytes leading to scaly patches. Secukinumab and ixekizumab are two biologic drugs inhibiting interleukin-17. Objective: We report the first case, according to Naranjo score, of a secukinumab-induced erectile dysfunction with severe plaque psoriasis that disappeared after switching to another anti IL17 drug (ixekizumab). Methods: A 45 years old man experienced erectile dysfunction during treatment with an anti-IL17. The adverse effect appeared after 60 days of treatment with secukinumab and rapidly disappeared after discontinuation of the drug. All necessary urologic exams were carried out. Re-administration of secukinumab, due to the exacerbation of psoriasis, caused the same sexual dysfunction after 60 days. Results: Switching to ixekizumab lead to a resolution of the erectile dysfunction and a complete skin clearance. Conclusion: We describe for the first time a sexual dysfunction possibly due to secukinumab and its resolution after the switch to another similar but different drug, highlighting the potential difference between anti-IL17A drugs.

Introduction: Mycophenolate Mofetil (MMF) is an immunosuppressive drug usually used in kidney transplants to prevent rejection. It has various adverse effects such as leucopenia, anemia, diarrhea but Mouth ulcers are rarely reported. Method: We present a case report of MMF-induced mouth ulcers in an African patient. Case Report: A 41-year-old African-male patient has painful oral ulcers which developed 5 months after kidney transplantation. The immunosuppressive maintenance regimen comprised Steroids, Tacrolimus and MMF. Result: These ulcers were firstly related to a fungic or viral infection so the patient was prescribed Fluconazole and Aciclovir without any improvement. Then, Tacrolimus blood level was checked and it was in a therapeutic range. Finally, we decide to stop MMF and the ulcers healed quickly. Discussion: Oral ulcers are frequently seen complications in immunosuppressant patient but are rarely described with MMF. These ulcers can become large and very painful and degrade patient's life quality. So when infections causes are excluded, we have to keep in mind that these ulcers can be a drug adverse effect.

Background: Infiximab has been shown to be effective in inducing and maintaining remission of intestinal bowel diseases. Infiximab has been associated with many adverse events. Articular manifestations are commonly reported, but they are of variable clinical expression and aetiology. Among them, inflammatory bursitis has rarely been described. Objective: Herein a case of inflammatory bursitis in a patient with Crohn’s disease after switching to biosimilar infliximab is reported. Case Report: A 41-year-old man with Crohn’s disease evolving from 3 years was referred to infliximab therapy at a dose of 5mg/kg because of an aggressive resistant perineal fistula. After 14 infusions of infliximab, the treatment was switched to infliximab biosimilar using the same dose and frequency of administration. Forty-eight hours after the second infusion, he developed an acute onset of muscle pain and stiffness on both of his shoulders. A musculoskeletal ultrasound was performed and revealed a hypoechoic widening of both subacromial bursae. It was more severe on the left side. Discussion: The diagnosis of non-infective sub-acromial bursitis secondary to infliximab infusion was made as the patient’s symptoms resolved rapidly without any antibiotics. Infliximab was definitively stopped and adalimumab was introduced. Conclusion: Musculoskeletal side effects of infliximab infusion are uncommonly reported. Among them, bursitis has been reported in only a few cases. Ultrasonography can help early diagnosis of bursitis. The time of occurring of this reaction regarding infliximab infusion, screening of Antibodies to Infliximab (ATI) and clinical outcome after drug discontinuation are the main helpful arguments.