Current Drug Safety - Volume 17, Issue 3, 2022

Background: Iodinated contrast media (ICM) are responsible for multiple side effects, especially hypersensitivity reactions. These reactions can either be authentic allergies or non-allergic hypersensitivity reactions. Skin tests (prick and intradermal tests) are simple to perform and can be of great help, especially if the ICM needs to be re-used. The aim of the study was to assess the characteristics of the patients in whom skin tests were performed and the results of these tests. Methods: This is a retrospective study from June 2014 to June 2019. All included patients had at least one episode of hypersensitivity reaction to ICM and underwent skin tests. Results: We included 35 patients aged 18 to 85 years. The iopromide was the most implicated ICM. The reactions were mainly cutaneous (n=30) and immediate (n=27). The skin tests were negative, except for two patients. The re-use of ICM occurred in 11 patients: 9 with an ICM other than the one suspected and two patients with the same ICM. Among these patients, 5 did not have any premedication. Two of them had a second hypersensitivity reaction, the first with another ICM and the second with the same ICM. Conclusion: One of the main pillars of allergic exploration is ICM skin testing, not only to prevent a recurrence, but also to allow patients to benefit from ICM re-use, which are sometimes essential.

Background: Compliance towards the requirements of labelling of dispensed medicine (LDM) among private primary health care facilities ensures appropriate use of medicines. Aims: This study aimed to examine the rate of compliance towards the requirements of LDM among retail pharmacies (RPs) and private medical clinics (PMCs). Methods: A cross-sectional study was conducted from April 2019 to January 2020 across all inspected premises in Sarawak. Publics who attended RPs and PMCs and have medicines dispensed have their medicine labels examined for compliance with the requirements of LDM upon exiting the premises. Their verbal consents were obtained and the compliance score was recorded into self- -developed data collection forms. The compliance rate was the percentage of requirements on the examined medicine labels that fulfill the requirements under Regulation 12 of Poisons Regulations 1952. Results: A total of 414 LDM were examined, with 135 from RPs and 279 from PMCs. The full compliance towards the requirements of LDM among RPs and PMCs were 23.7% and 41.6%, respectively. The median compliance score of PMCs (0.83) was significantly higher (P<0.001) than RPs (0.67). The requirements of LDM with the lowest compliance were name of medicine (53.1%), followed by name of patient (31.9%) and date of dispensing (25.6%). Conclusion: The full compliance rate on the requirements of LDM among RPs and PMCs were low. More stringent enforcement and public education on their rights for fully compliant medicine labels could improve the compliance.

Background: Extemporaneous compounding (EC) involves the preparation of a therapeutic product for specific patient need. However, there is a potential relationship between this procedure and the occurrence of health incidents (HI). The use of trigger tools increases HI identification. Objective: This study assessed the performance of EC as a trigger to detect potential health incidents arising from this procedure. Methods: A one-month observational and cross-sectional study was performed in internal medicine ward and intensive care unit of medium-sized hospital. Data collection was carried out in 5 stages: all triggered patients with dysphagia or enteral feeding tube with prescription of EC were included; EC executed in prescribed standardized drugs was observed; the procedure was compared with the hospital guide and scientific literature; HI monitoring and their evaluation using WHO and NCC MERP algorithms; a search for pharmaceutical alternatives (PA) that would avoid the observed EC. Results: 197 patients were recruited. Almost half of them were triggered by EC from 84 standardized drugs. 48 patients met the inclusion criteria. 28 adverse drug reactions, 01 therapeutic ineffectiveness, and 29 medication errors were identified. EC as a trigger tool showed a PPV value of 0.38. Only 24 drugs have PA available in the market, which could avoid one third of all observed EC. Conclusion: It was possible to detect potentially HI in one of two patients with enteral feeding tubes using EC as a trigger tool. The use of EC as a trigger tool contributes to identifying potential HI arising from drugs, which have not gotten pharmaceutical alternatives to be administered via enteral feeding tube.

Background: Cutaneous Adverse Drug Reactions (ADRs) are common and pose a serious challenge to physicians, especially in cases when the patient has many comorbidities, is polypharmacy, or self-administers over-the-counter medications. Objective: The objective of this study is to analyze the clinical pattern and incidence of cutaneous ADRs and perform causality assessment using the WHO-UMC scale and Naranjo’s scale. The severity of the reactions was determined by the Hartwig scale. Methods: This was conducted as a prospective observational study in patients admitted to SRM Medical College, Kattankulathur, Tamil Nadu, India, between November 2016 to August 2018 after obtaining Institutional Ethics Committee clearance of all adverse drug reactions reported at the hospital. Results: Of the 158 ADRs reported during the time period, 101 were cutaneous ADRs, of which the most common presentation was maculopapular rash (n=42; 41.58%). The most common drugs which produced cutaneous adverse reactions were antimicrobials (n=58; 57.42%) followed by NSAIDs (n=35; 34.6%). The causality assessment as per the Naranjo scale yielded 3.96% (4) cases as definite, 81.18% (82) as probable, and 14.85% (15) as possible, whereas the WHO scale yielded 9 (89.10%) certain, 64 (63.36%) probable and 28 (27.72%) possible cases. The severity of the cases determined as per the Hartwig scale yielded 82.17% cases as mild and 17.82% as moderate. Conclusion: It is important to recognise the ADRs at the right time and exert caution in future use. This can minimise harm to the patient both physically and financially and improve the outcome of the treatment.

Background: Vaccination of children has played a significant role in reducing early childhood morbidity and mortality from vaccine-preventable diseases; however, some factors act as deterrents in achieving adequate coverage in this susceptible population. Aims & Objectives: The study, therefore, aimed to identify vaccine-related determinants of childhood vaccination as well as determine the relationship between childhood vaccination status and body weight, height, and a child’s body mass index (BMI). Methods: The study was conducted using a cross-sectional design in which 608 caregiver-child pair was recruited sequentially by using a two-stage sampling technique. Structured questionnaires based on the SAGE vaccine hesitancy model were used to interview the participants. Elicited data was analyzed and categorical variables were presented in tables and charts as frequencies, while a chi-square test was used to test the association between the independent and dependent variables. Pearson’s correlation analysis was also done to determine the correlation between vaccination status and weight, height, and BMI of children. Results: The study showed that vaccination coverage was suboptimal (70.56%) in children and was below the expected target of 80%. Although a few (183, 30.10%) of the respondents claimed they would prevent the vaccination of their children due to the fear of needles, the majority (87.50%) will be willing to accept more vaccine doses for their children if there were no pain. While factors such as the experience of adverse reaction (X² = 13.22, df = 2, p<0.001), crying from pain (X² = 11.33, df = 2, p<0.001) and the scientific evidence of safety (X² = 34.63, df = 2, p<0.001) were significantly associated with a complete vaccination status, vaccination status was positively correlated with the weight (r=0.160, p<0.001), height (r=0.081, p=0.023) and BMI (r=0.214, p<0.001) of children in the rural community. Conclusion: Vaccination uptake and coverage can be significantly improved in children by designing and implementing interventional programs that target pharmaceutical and vaccine-specific factors acting as barriers in these rural communities.

Aims: Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Background: Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability. Objective: To evaluate the statistically significant difference (P<0.05) in the development of NMSC between HCTZ users and non-users and the correlation (P<0.05) between HCTZ use and NMSC. Methods: We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression. Results: We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC. Conclusion: In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.

Background: Detection of adverse drug reactions (ADRs) is a challenging matter for healthcare professionals who contribute significantly to the pharmacovigilance system through their participation inspontaneous reporting. Objective: The objective of this study was the detection and reporting of ADRs related to antibiotics in primary health care in the region of Peloponnese. Methods: A cross-sectional study was conducted in all national health system primary health units of the Peloponnese region in Greece. A self-administered questionnaire was distributed to a total of 404 physicians who provided services in these settings. Descriptive and multivariate statistical analysis was performed using the SPSS 25.0. Levels of significance were two-tailed and statistical significance was set at p =0.05. Results: 306 out of 404 physicians responded to the questionnaire, giving a response rate of 75.8%. 81.6% of physicians stated that they rarely observe ADRs related to antibiotic administration during their practice, 49.8% rarely report them, and 33.7% never report them. Non-serious side effects (42.5%), physicians’ workload (24.1%), and the lack of knowledge about the reporting obligation (20.6%) have been declared as the main reasons of non - reporting. In addition, physicians with ≤10 years of clinical practice rarely reported that they experienced ADRs after antibiotics’ administration compared to those with more work experience and specialized physicians (p= 0.001). Conclusion: ADRs reporting rates among physicians in primary healthcare are low. Changes in physicians’ attitudes are vital and can be achieved through consistent and continuous training programs as well as the inclusion of ADRs and pharmacovigilance themes into the tertiary education curricula.

Background: The growing numbers of patients with diabetes mellitus in Africa and the Middle East on antidiabetic therapies necessitate an understanding of adverse event (AE) reporting in these regions. Objective: The aim of the study was to provide an AE reporting overview in patients using insulin in Africa and the Middle East by characterizing and comparing individual case safety reports (ICSRs) features. Methods: The cross-sectional study analyzed ICSR data from a global pharmaceutical company’s pharmacovigilance database for January to December 2018 to describe and compare patient demographics, report sources, reporter types, ICSR seriousness, suspect products, indication for insulin use and AE preferred terms, by country. Results: Overall 7076 ICSRs were analyzed, 63.6% from the Middle East. Most ICSRs were nonserious (91.5%), from solicited sources (83.5%), and reported by consumers (70.7%). Patients from the Middle East were, on average, 34.2 years of age, had gestational diabetes mellitus as indication (64.3%), insulin detemir as suspect product (76.5%), and exposure during pregnancy as AE preferred term (89.1%). Patients from Africa were 48.1 years old on average, a higher proportion of type 2 diabetes mellitus was observed (52.2%), human insulin was the suspect product (51.6%), and blood glucose increased the AE preferred term (23.1%). Few macrovascular and microvascular complications were reported (< 1% in both regions). Associations between the region and patient age, gender, report sources, reporter types, indications for insulin use, suspect products, and AE preferred term were significant (p < 0.001). Conclusion: ICSRs features were region-specific and dependent on patient age, gender, report sources, reporter types, suspect products, and AE preferred terms.

Background: Anti-tumor necrosis factor-α (TNF-α) is a life-changing treatment leading to quality-of-life improvement. Nonetheless, this treatment is associated with a high risk of infection, especially tuberculosis. Objective: Our study aimed to determine the frequency of active tuberculosis in our patients with chronic rheumatic disease and treated with TNF-α. Methods: We conducted a retrospective study including patients with Rheumatoid Arthritis and Spondylarthritis diagnosed according to ACR/EULAR 2009 criteria and ASAS 2010, respectively, and treated with biological agents for at least 6 months. We collected data regarding tuberculosis screening and the occurrence of active tuberculosis during follow-up. Results: 82 patients were included (37 men and 45 women). The mean age was 42 ± 3.4 years. At inclusion, no patient had a medical history of tuberculosis. The diagnosis of latent tuberculosis infection was established in 17 patients (20.7%). Prophylactic treatment was prescribed in all these cases for three months. Two cases (2.4%) of active tuberculosis occurred under biologic (infliximab). It was two severe forms of tuberculosis. The first case had miliary tuberculosis associated with hepatic and peritoneal involvement. The second one had pleural tuberculosis. These two patients received anti-tuberculosis therapy, and the biological treatment was interrupted. Given the high disease activity, the anti-TNF-α was restarted after 3 and 4 months. There was no recurrence of tuberculosis after 7 years of follow-up. Conclusion: The use of TNF-α blockers is associated with a risk of disseminated forms of tuberculosis. Tuberculosis screening, which is recommended before the biological onset, is also necessary under this treatment. Restarting the anti-TNF-α after appropriate treatment of tuberculosis seemed to be safe.

Background: Phenytoin is the most commonly reported aromatic Anti-Epileptic Drug (AED) to cause Cutaneous Adverse Drug Reactions (CADRs). Cutaneous adverse drug reactions may be immune or non-immune mediated. It has been observed that predisposition is multifactorial and that gene mutations alone cannot be the cause. Objectives: In this study, we investigated the patient, disease, and drug-related risk factors associated with phenytoin-induced cutaneous adverse drug reactions in South Indian epileptic patients. Methods: This study was conducted as a single-center prospective case-control study over a period of 13 months. The Fisher’s exact test and multivariate binary logistic regression analysis were used to test the association of single and multiple variables, respectively. Results: This study comprised 26 patients with phenytoin-induced cutaneous adverse drug reactions (PHT-CARDs) and 32 phenytoin-tolerant controls with a mean age of 40.60±18.15 and 36.21±14.71 years, respectively. Among 26 phenytoin-induced cutaneous adverse drug reactions, 76.92% cases were mild-moderate reactions and 23.07% were severe. The onset latency period of these reactions ranged from 7-42 days. The multivariate analysis showed that multiple AEDs (OR =18.62, 95% CI 4.28-80.87, p=< .001) and comorbidities (OR= 5.98, 95% CI 1.33-26.78, p=.01) are risk factors for PHT-CADRs. PHT-SCARs were shown to be associated with previous allergy history (OR= 31, % CI 2.40-398.8, p=.008). Conclusion: The risk factors found to be associated with CARDs in South Indian Epileptic patients are multiple AEDs, comorbidities, and past allergic history. Therefore, physicians and other associated health care professionals should closely monitor the patients when phenytoin is employed.

Background: Anemia is one of the most common complications of Chronic Kidney Disease (CKD). The vast majority of Egyptian CKD patients are interchangeably treated with Darbepoetin Alfa (DPA) and Epoetin Alfa (EPA) to achieve and maintain target hemoglobin levels. Our study aimed to compare the efficacy and safety of DPA versus EPA for managing anemia amongst Egyptian patients with CKD undergoing dialysis. Methods: A multicenter, open label, randomized, prospective, parallel study was conducted. Patients with CKD undergoing dialysis with Hb level < 10 g/dl were enrolled. The primary efficacy endpoint was the change in hemoglobin concentration at the evaluation period (weeks 20-24). Prespecified adverse events of interest following administration, including blood transfusions requirement, blood pressure and hemoglobin excursions, the relationship between C - Reactive Protein (CRP) and hemoglobin, were assessed. Results: Only 98 of 104 enrolled patients completed the study, fifty patients received EPA, and 48 patients received DPA. Our results showed that a significantly higher percentage of patients who achieved target Hb level ≥ 11 g/dL in DPA treated group vs. EPA as well as the meantime to achieve Hb level ≥ 10 g/dL was shorter in DPA treated group. Safety profiles of both treatments were similar. A negative correlation was observed between serum CRP and hemoglobin level in hemodialysis patients. Conclusion: Our study showed that DPA was more effective and well tolerated in achieving and maintaining Hb levels with lower dosing frequency compared to EPA. Furthermore, CRP is recommended to be routinely measured where patients with higher CRP require high ESA doses.

Background: The majority of research in medication reconciliation has focused on the inpatient settings, and little is known about the outpatient settings, particularly in developing countries. As such, we conducted this study to evaluate direct clinical pharmacist involvement in medication reconciliation in outpatient specialty clinics in Iran. Methods: This prospective interventional study was conducted from September 2019 to February 2020 in a University-affiliated clinic in Iran. For 196 patients over 18 years of age who were scheduled for an appointment with a physician, medication reconciliation intervention was carried out by a clinical pharmacist. The number and type of unintentional discrepancies, their potential harm to the patients, their correlation with the patients' demographic and clinical characteristics, and the number of accepted recommendations upon the unintentional discrepancies by the clinicians were assessed and recorded. Additionally, patients' understanding of any change made to their current medication regimen was also assessed. Results: In total, 57.14% of patients had at least one or more unintentional medication discrepancies, with an overall rate of 1.51 (±0.62) per patient. This is while the patient understanding of their medication changes was inadequate in a significant proportion of the study patients (62.2%). Patients with older ages, lower educational levels, and a higher number of medications and comorbidities were at a higher risk of having unintentional discrepancies. The most common type of unintentional discrepancy was the omission of a drug, and almost half of the reconciliation errors might have had the potential to cause moderate or severe harm to the patient. From 145 recommendations suggested by the clinical pharmacist upon unintentional discrepancies, 131 cases (90.34%) were accepted and implemented by the clinicians. Conclusion: These findings further support the need for conducting medication reconciliation in outpatient settings to identify discrepancies and enhance the safety of patient medication use.

Background: Various cutaneous manifestations have been observed in patients with COVID-19 infection. However, the side effects on skin of the medications used for COVID-19, such as famotidine, have not been studied. Objective: This case series aims to present challenges in defining cutaneous manifestations of famotidine in the context of COVID-19. Case Presentation: We identified patients from Imam Khomeini hospital complex who were admitted to the ward due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), were taking famotidine and having cutaneous rash. Clinical data were obtained through observation and intervention. Discussion: We found 4 SARS-CoV-2 patients with cutaneous manifestations. The mean (±SD) age of the patients was 57±2 years, 3 patients were men, and their COVID-19 symptoms appeared 10±3 days before admission. The most common symptoms were cough and shortness of breath. All the patients were admitted for hypoxemic respiratory failure. Patients received famotidine for gastrointestinal prophylaxis, and all 4 patients developed Acral macular mountainous skin lesions in the upper and lower extremities, then we discontinued famotidine and lesions were recovered completely in all patients. Conclusion: These cases prompted us to inform clinicians about cutaneous complications of famotidine in COVID-19 patients.

Background: Acute bilateral blindness is an uncommon phenomenon that requires immediate diagnosis and action. The emergent evaluation should concentrate on an early distinction between ocular, cortical, and psychogenic etiologies. Objective: To present a case of cortical blindness without anosognosia due to the embolic occlusion of both posterior cerebral arteries (PCAs) and treated by intravenous and mechanical thrombolysis. Case Report: A 67-year-old woman was admitted to the Stroke Unit due to cortical blindness without anosognosia. At the admission to the hospital, an emergent computed tomography scan of the brain ruled out intracranial acute hemorrhage and showed subtle changes consistent with hyperacute ischemia of the left occipital cortex, while a CT angiography demonstrated the occlusion of the P3 segment of both right and left posterior cerebral arteries. The patient was treated with combined thrombolysis (intravenous and mechanical thrombolysis), obtaining complete revascularization and a significant clinical improvement. Conclusion: Even if there is no randomized controlled trial to compare the effectiveness and safety of mechanical thrombectomy (MT) to intravenous thrombolysis in patients with posterior circulation occlusion, the good outcome of this case encourages combined stroke treatments in posterior circulation stroke, even in case of mild but disabling neurological deficits.

Background: In this report, we describe a case of domperidone withdrawal in a woman with a history of major depressive disorder and obsessive-compulsive disorder (OCD), who experienced a recurrence of these disorders after stopping domperidone. Case Presentation: The symptoms improved after the restarting of domperidone and disappeared gradually as the drug was tapered and discontinued. Clinicians should consider domperidone withdrawal a differential diagnosis in women with a history of depression or anxiety who present with an acute onset of these symptoms following the abrupt discontinuation of domperidone. Conclusion: A gradual taper off of the drug may be effective in minimizing withdrawal symptoms and obviate the need for psychotropic drug use.

Background: DIGO or drug-induced gingival overgrowth occurs as a side effect of certain drugs. Until now, the etiology of drug-induced gingival overgrowth is not clearly understood. Among the calcium channel blockers, nifedipine has been shown to be most frequently associated with drug-induced gingival hyperplasia. Amlodipine is a comparatively newer calcium channel blocker that with a longer duration of action and lesser side effects as compared to nifedipine. There are only certain case reports of amlodipine-induced gum hyperplasia. Case presentation: We report a case of amlodipine-induced gum hyperplasia in a 66-year-old hypertensive patient taking amlodipine at a dose of 5 mg once a day. There was significant regression of gum hypertrophy after substitution of amlodipine by Losartan. Conclusion: Amlodipine is one of the commonly prescribed antihypertensive drugs, and gingival hyperplasia is one overlooked side effect in patients taking amlodipine. Awareness of this potential side effect of amlodipine may be helpful to reduce the anxiety of patients and the cost of diagnostic procedures.