Current Drug Safety - Volume 15, Issue 2, 2020

Background: Psoriasis is an autoimmune disease that ingeminates itself with the repeated proliferation of keratinocytes. It globally strikes a 2-5 % population on an average. Management of psoriasis remains a daunting task with various challenges influencing treatment, such as patient conformity and adherence to therapy, delicate patient profiles, psychological aspects, and skin as a barrier to topical delivery. The first part reviewed pathophysiology, triggering factors, and clinical classification. The second part reviewed all the therapies, such as topical, oral, biological, parenteral therapy, phototherapy, and the phyto-pharmaceuticals. Methods: The research data related to the existing and upcoming therapies for psoriasis treatment, several nanocarriers, existing marketed formulations, and detailed description of phytopharmaceuticals with their mechanism. Results: Topical therapy is the mainstay treatment option with limited adverse effects. Biological therapy has reformed conventional psoriasis treatment by being more efficacious and has increased patient acceptance due to decreased adverse events. Nanoformulations present an edge over conventional therapy due to improved anti-psoriatic effect and decreased side effects. Phyto-pharmaceuticals act as a complementary and alternative therapy for diminishing psoriasis symptoms. Conclusion: A rationalized cost-effective patient compliant therapy is required for effective management and complete cure of psoriasis.

Background: Disposal of pharmaceutical waste among patients is a global challenge especially in developing countries like Ethiopia. Improper medication disposal can lead to health problems and environmental contaminations. Therefore, the present study aimed to assess disposal practices of unused medications among patients in public health centers of Dessie town, Northeast Ethiopia. Methods: A descriptive cross-sectional study was conducted among 263 patients in four public health centers of Dessie town, Ethiopia from March to June, 2019. Face-to-face interviews using structured questionnaires were used to collect data from each study subject. Results: The majority of the respondents, 224 (85.17%) had unused medications at their home during the study period. The most commonly reported disposal method in the present study was flushing down into a toilet 66 (25.09%). None of the respondents practiced returning unused medications to Pharmacy. Moreover, 85 (32.31%) of the respondents reported never disposing their medications and believed that it is acceptable to store medications at home for future use. Conclusion: In the present study, there was a high practice of keeping medications at home and most of the disposal practices were not recommended methods. In addition, most of the respondents did not get advice from pharmacists and other health care professionals on how to dispose off unused medications. Hence, there is a need for proper education and guidance of patients regarding disposal practices of unused medications.

Background: Medications induced QT prolongation could cause ventricular arrhythmia, torsade de pointes, and death. Objective: The purpose of this study was to evaluate the magnitude of QTc interval prolongation as a result of levofloxacin treatment in patients admitted to cardiology wards. Methods: This was a cross-sectional study conducted in the coronary care units and general wards of the Imam Ali Heart Hospital in Kermanshah, Iran. The QTc interval was determined at baseline and after 72 hours of levofloxacin administration. Changes in the QTc interval before and after the levofloxacin prescription were determined. Results: The mean age of recruited patients was 63.26 ± 14.56 years. More than 80% of patients who received levofloxacin experienced QTc prolongation. The QTc interval was increased significantly after levofloxacin administration (15.68 ± 26.84 milliseconds) (p<0.001). These changes remained significant after excluding medications with QTc lengthening properties (p<0.001). Conclusion: Treatment with levofloxacin in patients with heart disease increases the risk of QT prolongation.

Background: The adoption of guideline recommendations of pharmacotherapy to improve the clinical course of Heart Failure (HF) remains below par. Our objective is to evaluate the impact of clinical audit on adherence to the Guideline-Directed Medical Therapy (GDMT) in patients admitted with acute heart failure with reduced ejection fraction (EF). Methods: A prospective interventional study was conducted over a period of 12 months from June 2018 to May 2019 in all patients admitted with acute heart failure with reduced ejection fraction. The discharge prescriptions of patients who met the inclusion criteria were audited for appropriateness in the usage of neurohormonal blockers and Ivabradine, by a clinical pharmacist on a monthly basis. Audit results were presented to the practicing physicians every month and feedback was given. Results: Discharge prescriptions of 716 patients who presented with HF were audited for the reasonable or unreasonable omission of neurohormonal blocking drugs. The first-month audit revealed that the unreasonable omission of Angiotensin-Converting Enzyme Inhibitors/ Angiotensin Receptor Blockers/ Angiotensin Receptor Neprilisin Inhibitors ( ACEI/ARB/ARNI), Betablockers and Mineralocorticoid Receptor Antagonists (MRA) were 24.5%, 13.1%, and 9.09% respectively, which reduced to nil at the end of the study period (p=0.00). Initiation of Ivabradine before prescribing or achieving the target dose of Betablocker was noted in 38.18% of patients in the first month, which was also reduced to nil (p=0.00) at the end of the study. Conclusion: This study reveals that periodic clinical audit improves adherence to GDMT in patients admitted with heart failure with reduced ejection fraction.

Background: Efficiency and accuracy for signal detection and evaluation activities are integral components of routine Pharmacovigilance (PV) practices. However, an Individual Case Safety Report (ICSR) may consist of a variety of confounders such as Concomitant Medications (CM), Past Medical History (PMH), and concurrent medical conditions that influence a safety officer’s evaluation of a potential Adverse Event (AE). Limited pharmacovigilance systems are currently available as a tool designed to enhance the efficiency and accuracy of signal detection and management. Objective: To introduce a systemic approach to make critical safety information readily available for users in order to discern possible interferences from CM and make informed decisions on the signal evaluation process – saving time while improving quality. Methods: Oracle Empirica Signal software was utilized to extract cases with CM that are Known Implicating Medications (KIM) for each AE according to public regulatory information from drug labels – FDA Structured Product Labeling (SPL) or EMA Summary of Product Characteristics (SPC). SAS Enterprise Guide was used to further process the data generated from Oracle Empirica Signal software. Results: For any target drug being evaluated for safety purposes, a KIM reference table can be generated, which summarizes all potential causality contributions from CMs. Conclusion: In addition to providing standalone KIM table as reference, adoption of this concept and automation may also be fully integrated into commercial signal detection and management software packages for easy use and accessibility and may even lead to reduced False Positive rate in signal detection within the PV space.

Background: Central Nervous System (CNS) depressants like antipsychotics, opioids, benzodiazepines and zolpidem are frequently used by patients of a wide range of ages. Uncertainty remains about their effect in very old adults (>80 years old) and their potential for pharmacodynamic and pharmacokinetic drug-drug interactions in this population. Objective: To assess if the use of CNS depressants is associated with a higher risk of hospitalization due to community-acquired pneumonia (CAP) in very old patients. Methods: In this prospective study, 362 patients over 80 years of age who had been consequently admitted to the general ward of a teaching hospital were examined. Each patient was assessed, by our pharmacovigilance team within 24 hours of admission, to identify outpatient medication use and potential drug-drug interactions. Results: The overall use of CNS depressants as a group was not associated with a higher risk of admission due to CAP in very old patients (55% vs. 49%; OR=1.28 [0.76-2.16], p=0.34). However, the use of antipsychotics was associated with a higher rate of admissions due to CAP in this population (OR=1.98 [1.10-3.57], p=0.02). No association was seen between opioids (p=0.27), zolpidem (p=0.83), or benzodiazepines (p=0.15) and the rate of admissions due to CAP in these patients. Moreover, pharmacodynamic or pharmacokinetic interactions leading to CNS depression were equally found in patients admitted for CAP and those admitted for other reasons. Conclusion: The use of antipsychotics in very old adults was associated with an increased risk of hospital admission due to CAP. This suggests that the use of these medications in this population should be done with caution. No association was observed with opioids, benzodiazepines and zolpidem with the latter outcome.

Background: The success of a reporting system of adverse drug reaction (ADR) depends on the knowledge, attitudes, and practices of the health care professionals. However, due to a lack of knowledge and poor contribution by healthcare workers, ADR remains underreported. To improve safety, proper identification and ADR reporting is necessary. Objective: This study was carried out to determine knowledge, attitude, and practices of ADR among physicians and pharmacists working in Pakistan and the factors which encourage and discourage effective reporting. Methods: A cross-sectional study was conducted using a pretested questionnaire. Questionnaires were distributed among 333 physicians and 34 pharmacists with a 95.5% response rate. The Statistical Package for Social Science (SPSS) was used for data analysis. Results: Pharmacists have more knowledge regarding ADR compared to physicians (47.1% vs. 13.8%, p < 0.001). Pharmacists also have a positive attitude compared to physicians (97.1% vs. 76.3%, p < 0.001). No significant difference was noticed in ADR practice by physicians and pharmacists (12.3% vs. 11.8, p = 0.92). The seriousness of ADR was the main factor that encouraged nearly all pharmacists to report, whereas among physician’s, seriousness and the unusualness of reaction, the new drug involvement, and confidence in diagnosis were the factors which encouraged them to report ADR. Conclusion: Overall, pharmacists had more knowledge and a positive attitude regarding ADR reporting compared to physicians, but practices of ADR reporting remained the same among both. Therefore, it is suggested that educational interventions, along with training programs, should be developed.

Rationale and Objective: Proton pump inhibitor (PPI) is one of the most widely prescribed medicines and commonly used in gastric related disorders and there is a huge need to analyze the irrational use of PPI in a country like India. The present study was designed to describe the rational drug use and cost comparison analysis of PPI in a rural tertiary care hospital. Methodology: A prospective observational study was performed among 253 inpatients for a period of 9 months after getting ethical approval. Those who received the PPIs for any of its indications were included in the study without any gender or age restriction. US FDA guidelines were used to analyse the appropriateness of the drug use and cost comparison analysis of the branded versus generic PPIs was also performed. Findings: Among the 253 inpatients, the majority (62%) were male and the mean age was 46±19 years. Mean hospital stay and the number of drugs in prescription were found to be 4.0 ± 1days 4.39 ±1.16 items, respectively. Pantoprazole (76%) was the most prescribed PPI even though the majority (57%) of the patients treated outside the FDA approved indication. Drug interaction has been reported in 14% and ADR in 9% of the population. The average cost of hospital stay estimated as 207.96+149.57 INR, and potential cost saving of INR 41582 was observed with generic replacement. Conclusion: The study inferred irrational drug use of PPI still prevalent, that too without considering the economic impact of it on general populations. Healthcare practitioners should be aware and cautious while prescribing the PPI to identify the actual need and to choose the most cost-effective alternative 1.

Background: Lamotrigine is a phenyltriazine medication that has been approved by the United States Food and Drug Administration as monotherapy and as an adjunctive agent for the treatment of seizure disorder. It was later approved by the FDA for the treatment of bipolar disorder. Lamotrigine is generally well tolerated by patients, but some serious symptoms can occur during treatment. These severe side effects include rashes and multi-organ failure. Lamotrigine has also been associated with the development of mental status changes, frequently when used concurrently with other medications that may impact the metabolism of lamotrigine. Objective: To present the case of a 65-year-old man being treated with lamotrigine and valproic acid who developed mental status changes after the addition of sertraline to his medication regimen, and to compare this case to existing cases reported in the literature. Discussion: Our case adds to the existing literature by demonstrating that patients may experience adverse medication effects despite lamotrigine levels that are normally considered to be in the therapeutic range, highlighting the importance of clinical correlation when obtaining medication levels. Conclusion: Clinicians should use caution interpreting lamotrigine levels when working up delirium, as normal levels may not rule out the development of lamotrigine toxicity.

Background: Dabigatran is a novel oral anticoagulant molecule which is a direct thrombin (Factor IIa) inhibitor and is used for prevention of stroke and systemic embolism. It is easy to administer as compared to warfarin therapy as it does not require routine laboratory monitoring and has fewer drug interactions. Objective: To present a rare case of oral ulcers secondary to dabigatran in a patient with deep vein thrombosis. Case Report: A 68-year-old female presented with painful oral ulcers, retrosternal pain and difficulty in swallowing. She had been taking capsule Dabigatran for the prevention of systemic embolism for 2 months. She had experienced symptoms of onset taking dabigatran for 7 days. Clinical examination revealed three tender, well-defined, clean looking ulcers of various sizes present over the dorsum of the tongue. Dabigatran was withdrawn and the patient was on oral proton pump inhibitors. Patient showed remarkable improvement in oral ulcers after 2 weeks. Conclusion: Patient education and counseling should be done regarding this side effect of dabigatran and proper intake of this medicine.

Background: Psoriatic Arthritis (PsA) is a chronic inflammatory disease that may affect different joints. Sarcoidosis is a Th-1 cell-related chronic granulomatous disease characterized by non-caseating granuloma formation. The coexistence of both the diseases is a rare entity. Ustekinumab, an IL12 / 23 inhibitor, has shown efficacy and safety in the treatment of PsA. Objective: This study presents a case with ustekinumab-induced sarcoidosis in a patient with PsA. Case Report: A 52 years old female patient with complaints of pain and swelling of the wrists, MCP, PIP and DIP joints and skin lesions was referred to our Rheumatology clinic. On her medical history, she had been under follow up for 5 years with the diagnosis of psoriasis and one year ago, she started to receive ustekinumab prescribed by a dermatologist. On physical examination, she had psoriasis skin lesions and arthritis of both wrists, MCP, PIP, DIP joints. Bilateral hilar lymphadenopathies were detected in the chest X-ray and thorax computed tomography. In laboratory tests, acute phase reactants and serum angiotensin-converting enzyme levels were high. Endobronchial ultrasonography biopsy was performed and non-caseating granuloma consistent with sarcoidosis was reported. Ustekinumab was discontinued, methotrexate and low-dose corticosteroid were started. The patient was clinically stable in the 6th month of the treatment and the findings were regressed. Conclusion: Sarcoidosis development appears to be a new paradoxical effect of ustekinumab therapy, being another biological agent.