Current Drug Safety - Volume 13, Issue 2, 2018

Background: Epistaxis is an active nose bleeding with a population occurrence of approximately 60%. Although epistaxis is a common clinical complaint, the majority of the cases are benign and caused by local induced factors (e.g., trauma and local inflammation). Nevertheless, it is also recognised that epistaxis can be induced after some drugs intake. Aims: Due to the increasing use of drugs or drug combinations that potentially may induce epistaxis, this review aims to alert healthcare professionals for this often neglected adverse drug effect and its possible complications. Methods: A comprehensive literature search was performed on PubMed and Google Scholar databases, considering the literature published from January 1985 to December 2015, using medical terms related to drug-induced epistaxis, nosebleeds and nasal blood supply. Results and Discussion: As expected, anticoagulant and antiplatelet drugs are the main pharmacotherapeutic agents associated with epistaxis, particularly warfarin, dabigatran, rivaroxaban and aspirin. However, it was reported that some selective serotonin reuptake inhibitors, intranasal corticosteroids, certain antibiotics and other drugs or drug associations can also be responsible for nosebleeds. Although most of these epistaxis episodes are mild to moderate, being spontaneously reversed or requiring only minor medical approaches to control it, there are several case reports, as well as retrospective and prospective studies, documenting severe epistaxis episodes after specific medicines intake. In these cases, some invasive medical interventions are demanded to manage the bleeding and avoid life-threatening consequences. Conclusion: This work provides an integrated and comprehensive review on drug-induced epistaxis bridging the gap in the current scientific literature addressing this topic. Therefore, the scientific information gathered and discussed will be valuable to raise awareness among doctors and pharmacists for this drug-related problem, as well as to promote their active pharmacovigilance and reinforce patient education.

Background: Sodium glucose co-transport 2 inhibitors (SGLT2-i) are the new class of antidiabetic medications which are recently approved (2013) by the Food and Drug Administration (FDA) for the treatment of diabetes. These inhibitors block the SGLT2 protein which involved glucose reabsorption from proximal renal tubule resulting in increased glucose excretion and lower blood glucose levels. These inhibitors exert favourable effects beyond glucose control such as consistent body weight, blood pressure and serum uric acid reductions. Canagliflozin, Dapagliflozin and empagliflozin belong to the class of SGLT2 inhibitors. Results and Conclusion: All these drugs are giving promising results in the treatment of diabetes mellitus, but emerging data from post-marketing studies indicate their adverse effects such as diabetic ketoacidosis, genital and urinary tract infection, cancer, bone fracture and foot and leg amputation. Thus, there is a need for better understanding the risk profile of SGLT2 inhibitors. In this review, we have compiled the risk profile of SGLT2 inhibitors by collecting information from various sources such as case reports, published literature and from various regulatory websites. Further, the proposed mechanism of risks has also been discussed.

Background: Electronic Cigarettes (ECIGs) are devices with a heating element which produces aerosol for inhalation. They have been propagated as a healthier alternative to tobacco smoking and a potential device for smoking cessation, despite non-documentation of their long-term adverse health effects. Objectives: With the glorification of ECIG, its use has increased even among non-tobacco users. This makes it critical to understand and discuss a true picture of safety and utility of ECIGs by reviewing the literature. Methods: Literature search for narrative review was done on PubMed, Scopus and Web of Science databases using the keywords viz electronic cigarette, e-cigarette, electronic nicotine delivery systems, NRT, vaping and electronic nicotine delivery device. The review was sub-categorized into four themes (potential role in smoking cessation, chemicals in the smoke of traditional cigarette and ECIGs, pharmacology of nicotine delivery via ECIG and current regulatory status across the globe). Results: Search revealed a total of 40 articles out of which 29 were included in the review. ECIGs achieved modest cessation rates with benefits of behavioral and sensory gratification. On the contrary, in many studies where ECIGs were introduced as an intervention, participants continued to use them to maintain their habit instead of quitting. A total of 22 toxic substances apart from nicotine were reported in liquid of ECIG cartridges and its emissions. Many compounds had lower concentrations in ECIG compared to tobacco smoke. There existed a wide variation in the content of ECIG cartridges and strengths of nicotine in refill solutions. It has been observed that the second generation ECIGs delivered nicotine with a similar kinetic profile as conventional cigarettes. In 2013, US FDA gave market authorization to ECIG as substitutes for quitting smoking and cigarette substitutes. The United Kingdom also advocates ECIGs as a medicinal quit aid but bans it from workplaces and other public spaces. India along with many other countries still need to come up with a formal regulatory stand regarding ECIGs. Conclusion: There is a need to conduct large long-term global clinical trials in real life settings to ascertain the potential uses, adverse effects of ECIG and achieve harmonization of nicotine solution concentration.

Background: Acute biochemical changes, hepatotoxicity, nephrotoxicity and frequency of infections are common in diffuse large B-cell Lymphoma patients undergoing Cyclophosphamide, Doxorubicin, Oncovin (Vincristine) Prednisone (CHOP) and Rituximab plus CHOP chemo cycles. Eventually, it leads to prolonging hospital stay and suspending the next chemotherapy cycles. Aims and Objectives: The objectives of our study were to determine the changes in biochemical disturbances induced by CHOP or RCHOP and second objective was to compare the effect of CHOP with or without rituximab on the incidence of the infections such as (Cytomegalovirus, Herpes Simplex Virus and Varicella-Zoster virus), bacterial infections and tuberculosis. Materials and Methods: Files were prospectively reviewed during the tenure of 2014-2016. Participants aged greater than or equal to 18 years old with a known case of DLBCL undergoing CHOP or RCHOP chemotherapy were allowed to be included in the study. Baseline and posttreatment patients profile of blood chemistry, liver functions test was collected and compared with the Common Terminology Criteria for adverse events v3.0 2009 CTCAE 2009 and the data regarding infection of Cytomegalovirus, Herpes Simplex Virus and Vericella-Zoster virus, bacterial infections and tuberculosis were drawn from the participant's profile. Results: Patients treated with CHOP therapy showed a significant difference of Alkaline Phosphatase (ALP) (p-value 0.009), direct bilirubin (p-value 0.034) and serum glutamic-pyruvic transaminase (SGPT) (p-value 0.004). Bacterial Pneumonia was only 1 (5%) and 1 (5%) CMV reported positive after the R-CHOP. Conclusion: We propose that liver profile including (bilirubin, SGOT and SGPT) Urea, Creatinine and electrolytes should strictly be considered if found deranged before every treatment cycle and suspend chemotherapy in case of moderate or severe toxicity.

Background: In clinical trials of Pneumococcal Conjugate Vaccines (PCV), some adverse events have been reported more frequently in the PCV vaccinated. Ten-valent PCV (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010. Objective: We conducted an ecologic register-based study to investigate further the reported adverse events after PCV. Methods: This study included data obtained from the Finnish nationwide, population-based registers. First diagnoses of febrile seizures, breath-holding, urticarial rash, asthma and Kawasaki's disease were included as outcomes obtained from the hospital discharge register. Data from Finnish Population Register during 2000-2014 for children age from 3 months to 10 years were used to estimate annual incidence rates. Incidence rate ratios of the outcomes were calculated between the target cohort of children eligible for PCV10 during 2010-2014 and a reference cohort before the NVP introduction (2004-2008). Results: No increases in the incidence of the adverse events after PCV10 introduction were found except for urticarial rash (incidence rate 2.48 vs. 1.60/1000 pyrs; incidence rate ratio, 1.54;95% CI 1.42-1.67). This increase was seen also in the unvaccinated older age groups in the post-vaccination era. The higher incidence of urticarial rash after the PCV10 introduction was due to the inclusion of diagnoses made in general medicine specialty in the discharge register because of a concomitant administrative change. Conclusion: The results do not support public health concerns related to the previously reported adverse events. Concomitant changes in health care administration and coding introduced bias, which was controlled after further evaluation of the data. We consider this register-based approach with realworld data feasible in the signal validation process after any signal detection.

Background: In the recent past, many third-generation antiepileptic drugs (AEDs) including Pregabalin (PGB) were launched for the treatment of diverse forms of epilepsy with better efficacy and safety profile than first-and-second-generation AEDs, but their teratogenic safety has not been established so far. Objective: The present study has been undertaken to evaluate the reproductive and teratogenic potential (external and skeletal) of a novel and third generation AED, PGB in pregnant albino rats. Methods: In this study, pregnant subjects were exposed to clinically relevant doses (41, 82 and 123 mg) of PGB from gestation days 6-20, and sacrificed on GD-21, and their fetuses were collected and examined to identify the birth defects and skeletal anomalies. Results: This study revealed that prenatal exposure to PGB induced dose-dependent substantial fetal resorptions, litter size, fetal length and weight; and variety of minor external and internal malformations in fetuses predominant with limbs, tail, eyes, abdomen including hemorrhages, and poor skeletal ossification. Conclusion: Thus, PGB was found to be teratogenic in rats at equivalent therapeutic doses, hence precaution should be taken before prescribing PGB to pregnant women with epilepsy.

Objective: The aim of this study is to evaluate the potentially inappropriate medication use and medication compliance in elderly patients who buy prescribed drugs from a pharmacy in Ankara. Methods: In this cross-sectional field study, 200 older people who bought prescribed drugs from a pharmacy which is close to several hospitals in Ankara in April 2016 were chosen as random sample. A questionnaire consisting of questions related to socio-demographic characteristics, health status, drug use of elderly and Morisky Green Levine Medication Adherence Scale (MGLS) was used to collect data. The appropriateness of the drugs prescribed for elderly was determined by the pharmacist according to Beers criteria. The data were evaluated by descriptive statistics and Chi-Square test. Results: 57.4% of the 200 elderly patients in the study are women and the mean age is 72.55 ± 6.34 years; 72.6% of them are below high school. When the medication compliance was examined, 36.3% of them did not comply with the drug treatment according to MGLS. It was determined that having sufficient information about the drug, education level, occupation and polymorbidity affect medication adherence (p <0.05). When the appropriateness evaluated according to Beers Criteria, 41.7% of the subjects were prescribed potentially inappropriate medications (PIM). According to the analysis, the number of drugs prescribed and the type of the chronic disease have effects on the inappropriate prescription (p <0.05). Conclusion: According to the study, the prevalence of inappropriate medication use in the elderly is higher than the medication non-adherence.

Bilateral pitting edema is rare adverse drug reaction observed in the psychiatry department. Drug related pedal edema is most commonly seen with ACE inhibitors, non-steroidal antiinflammatory drug, and calcium channel blockers. But pitting edema with Sodium valproate is very rare. Here, we report two cases of Sodium valproate-induced bilateral pitting edema.

Introduction: Topiramate is a well-known anticonvulsant drug with a broad spectrum of actions. It has been proposed in the treatment of several types of epileptic seizures both in monotherapy and in add-on. Its usage has been extended to other disorders including migraine, essential tremor, obesity, alcohol and drug addiction. The most frequent side-effects of topiramate include dizziness, somnolence, insomnia, and ataxia. Paraesthesia, metabolic acidosis, kidney stones, hypohidrosis, cognitive impairment and eye symptoms have also been reported. Case Report: We report on a girl affected by epileptic seizures treated with levetiracetam for five years. Due to worsening of the seizures, the dosage of this drug was increased and afterwards lowdosage topiramate was initiated. After 12 days from the introduction of topiramate, the girl began to present neurologic signs including limbs rigidity, pain, incoordination and flexed fingers. Gradual withdrawn of the topiramate resulted in progressive resolution of the symptomatology. This clinical episode could represent a probable topiramate-related side effect (Naranjo score 5), never reported before in this form.

Background: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), also known as Lyell's syndrome, are rare and life-threatening conditions, for which etiopathogenesis, as well as pharmacotherapy, is yet unclear. Case Report: A 45-year-old male patient by chance on re-exposure to Ofloxacin developed Severe Cutaneous Adverse Drug Reaction (SCADR), diagnosed with toxic epidermal necrolysis. His comorbid conditions and systemic complications of TEN lead him to death. In developing countries, where antibiotics especially fluoroquinolones are widely prescribed, a physician should be now vigilant for such kind of SCADRs because of increasing numbers of such kind of reports.

Background: Salsalate may offer many advantages over other non-steroidal antiinflammatory agents in patients taking warfarin, however a drug-drug interaction may occur which has not been reported in the medical literature or by the manufacturer of salsalate. Objective: To report a case of warfarin potentiation associated with salsalate treatment, which resulted in bleeding. Method: Clinical review of the course of a patient, who was stable on warfarin when salsalate therapy was added for chronic pain. Case Report: A patient taking stable doses of warfarin for over 1 year (with good control) was prescribed salsalate 3 g/day for pain in his knee and lower back. Approximately 1 month later he presents to the anticoagulation clinic with bruising and an International Normalized Ratio (INR) of 6.8. The patient had a good response to his salsalate therapy and wanted to continue it. The warfarin was held for 3 days and dose lowered by 50 %. His bruising then subsided and he had good control of his warfarin therapy with INRs ranging from 1.9 to 2.2 over the next 4 months. The patient was then lost to follow up. Conclusion: This case illustrates a strong association between starting salsalate and subsequent potentiation of warfarin, which heretofore has not been reported in the medical literature.

Background: Treatments of patients with amlodipine (a calcium channel blocker, CCB) overdose/poisoning remain challenging and death is certain if not intervened timely. Furthermore, for the society, the availability and common use of this drug can drive more vulnerable groups, especially children, towards an accidental/suicidal poisoning. Case Report: Herein, we describe the case of an 18 year-old-adolescent girl who took 150 mg of amlodipine with the suicidal intentions and was admitted in our hospital approximately 4-hours after the ingestion. She developed circulatory failure and tachypnea. Decontamination, calcium, glucagon, and dual vasopressors were started, however, persistent hypotension led to the initiation of hyperinsulinemiceuglycemia therapy. She recovered fully and discharged without any complications in few days. This case educates not only about the successful use of variant drugs in the management of CCB overdose/poisoning, but also calls for the attention of the society for a safe storage of often used drugs, especially away from the children/adolescents.