Current Drug Safety - Volume 13, Issue 3, 2018

Background: Immune checkpoint inhibitors are a new promising class of antitumor drugs that have been associated with a number of immune-related Adverse Events (AEs), including musculoskeletal and rheumatic disease. Methods: We searched Medline reviewing reports of musculoskeletal and rheumatic AEs induced by immune checkpoint inhibitors. Results: Several musculoskeletal and rheumatic AEs associated with immune checkpoint inhibitors treatment are reported in the literature. In particular, arthralgia and myalgia were the most common reported AEs, whereas the prevalence of arthritis, myositis and vasculitis is less characterized and mainly reported in case series and case reports. Other occasionally described AEs are sicca syndrome, polymyalgia rheumatica, systemic lupus erythematosus and sarcoidosis. Conclusion: Newly induced musculoskeletal and rheumatic diseases are a frequent adverse event associated with immune checkpoint inhibitors treatment.

Background: Recently, Food and Drug Administration (FDA) has approved Dulaglutide (GLP-1 analog) for the treatment of type 2 diabetes mellitus. However, regarding Adverse Drug Reactions (ADRs) of Dulaglutide in a large group of population, very less information is available. Thus, in the present investigation, we tried to find out the risk and benefit profile of Dulaglutide. Materials and Methods: The data related to risk and benefit profile of Dulaglutide has been extracted from various sources like Pub-Med, Regulatory Websites of various agencies, Clinical trial registry etc. from Sep 2014 (first approval) to Feb 2018. A total of 182 studies have been published from Sep 2014 to Feb 2018 regarding Dulaglutide. After inclusion and exclusion criteria, 25 studies have been selected for risk and benefit analysis. Results: The results of the current study have shown the various therapeutic benefits of Dulaglutide (reduces weight, decreases progression of nephropathy, reduces incidence of myocardial infarction, reduces blood pressure etc.) in the treatment of type 2 diabetes mellitus. However, emerging evidence has also indicated the various risks associated with Dulaglutide such as septicemia, malignant neoplasm, coronary artery disease and pancreatic cancer. Conclusion: In conclusion, Marketing Authorization Holder (MAH) and Regulatory Authorities (RAs) should consider these safety issues in future.

Introduction: 36 out of 100 cases of retrosternal chest pains are due to oesophageal pathologies, and Pill-induced Oesophagitis (PIO) is one of them. PIO can present as retrosternal chest pain associated with various Gastrointestinal (GI) symptoms and require a high index of suspicion. PIO is a clinical diagnosis; and oesophagogastroscopy is required for confirmation of the diagnosis, to find out complications of PIO and to rule out other oesophageal disorders. Our aims of the present study were to study clinical profile, risk factors and endoscopic features of PIO. Materials and Methods: We have done a cross-sectional study of 1000 patients with acute retrosternal chest pain, and all patients of suspected upper gastrointestinal system involvement were subjected to oesophagogastroscopy. Patients having a history of pill ingestion followed by retrosternal chest pain with GI symptoms of less than 10 days duration and having typical endoscopy findings like kissing ulcer, multiple small discrete ulcers or erosion of esophagus were diagnosed as PIO after excluding other oesophageal pathologies. Results and Conclusion: Among 1000 retrosternal chest pain patients, 450(45%) cardiovascular, 255(25.5%) respiratory, 248(24.85%) upper GI and 47(0.47%) had other system involvement. Among 248 GI patients, the frequency of symptoms was as follows: Pinpoint localized odynophagia (8.46%), non-localised odynophagia (12.09%), nausea (62.09%), vomiting (44.35%), dysphagia (3.62%), dyspepsia (13.70%) and hematemesis (0.8%). PLO, dysphagia, and hematemesis were significant symptoms of PIO (p<0.05). Endoscopic findings suggestive of PIO such as kissing ulcer, multiple small discrete ulcers, oesophageal erosions were observed in 91.30%, 47.83%, and 34.78% patients, respectively. Involvement of the middle third of esophagus was present in 74.19% and the lower third in 25.81% patients. Most of the patients with PLO had kissing oesophageal ulcer seen on endoscopy (pvalue =0.0002). The habit of consuming pill with less than 100 ml of water and consumption of night pill dose 10 minutes or less before sleeping were observed as significant risk factors for PIO (p value<0.05). PLO is a newly established and highly specific symptom of PIO of our study and it matches with kissing ulcer of the esophagus by endoscopy.

Background: Studies of the adverse effects of antidepressants tend to focus on biological symptoms. The prevalence of suicidality and withdrawal effects are currently a source of controversy. Objective: To directly ascertain the experiences of an international sample of antidepressant users. Methods: An online survey asked adult antidepressant users whether they had experienced 20 adverse effects ‘as a result of taking the antidepressant’, and if so, to what degree of severity. 1,431 people, from 38 countries, responded. Results: 61% of the respondents reported at least ten of the 20 adverse effects, most commonly: ‘Feeling emotionally numb’ (reported by 71%), ‘Feeling foggy or detached’ (70%); ‘Feeling not like myself’ (66%), ‘Sexual difficulties’ (66%), ‘Drowsiness’ (63%), and ‘Reduction in positive feelings’ (60%). ‘Suicidality’ as a result of the drugs was reported by 50%. Withdrawal effects were reported by 59%, and ‘Addiction’ by 40%. Rates of adverse effects were higher for those prescribed multiple antidepressants and those who also took antipsychotics. Younger age and longer use of ADs were positively related to total adverse effects. One third did not recall being told about any side effects by the prescriber. Less than 5% were told about suicidality, emotional numbing, withdrawal effects or addiction. Conclusion: Asking people directly reveals far higher rates of adverse responses to antidepressants than previously understood, especially in the emotional, psychological and interpersonal domains. Given recent findings that antidepressants are only marginally more effective than placebo, the findings of the current study imply a cost-benefit analysis that cannot justify the extremely high prescription rates for these drugs.

Background: Different combinations of Direct Antiviral Agents (DAAs) have been used against different Hepatitis C Virus (HCV) genotypes and in different types of patients. Despite being effective and characterized by a very low rate of adverse effects in clinical trials, few data are available on adverse events in real life studies. Objectives: The aim of this study was to identify the incidence and pattern of Adverse Drug Reactions (ADRs) caused by DAAs; daclatasvir and sofosbuvir and their combination with ribavirin and to assess the causality and the severity of the reported ADRs. Methods: A prospective observational study was conducted over six months at treatment HCV center of Health Insurance Hospital in Fayoum Governorate, Egypt. A pre-tested, interviewed structured questionnaire was used by authors to gather required data from 345 enrolled patients regarding demographics, co-morbidity and ADRs. Causality and severity of ADRs were assessed. Results: According to our data. we have found that 75.7% (261out of 345) patients reported 36 different ADRs involving different systems, of these 1.2% experienced Serious Adverse Events (SAEs), including three deaths (0.9%). A majority of ADRs were more significantly reported with ribavirin-containing regimen. Out of 345 patients, 23.5% have comorbidities. Among them, 92.6% reported ADRs. Causality assessment of ADRs by WHO–UMC criteria revealed that 38.89% were probable while 61.11% were possible. Conclusion: New antiviral drugs require careful follow-up of any significant adverse event that may occur and can affect adherence. Special population as the elderly and those with comorbidities should always be managed with caution to avoid development of serious side effects.

Background: Acute Eosinophilic Pneumonia (AEP) is a rare, potentially fatal disease often characterized by a short febrile illness, hypoxemic respiratory failure, diffuse pulmonary opacities and evidence of pulmonary eosinophilia. AEP can be idiopathic, but has documented associations with multiple drugs. Case Report: We present the first case highlighting Sertraline specifically as a cause of drug-induced AEP in the English literature.

Background: Given the growing use of off-label in pediatric practice, there is a growing interest on pharmacovigilance programs monitoring the occurrence of adverse drug reactions related to off-label drug prescription in childhood. Patients and Methods: The results of a one-year program of pharmacovigilance issued in the Sicilian Region, Italy, are herein presented. The study involved 6 pediatric and neonatal centres and prospectively reviewed the prescriptions of 5,060 patients, who were stratified for age (newborn, infant, children, adolescents). Results: A total of 14,916 prescriptions were issued for 5,060 patients. Among them, 454 patients [8.97%] received at least one off-label drug. Among the off-label treated patients, 255 [56.2%] were newborns. Anti-infective drugs were the most frequent off-label used drugs, followed by drugs for alimentary tract and metabolism and drugs for blood or blood forming organs. Ninety adverse drug reactions were recorded [1.78% of the total patients]. They occurred after an off-label prescription in 33 out of 90 [36.7%], while those occurring after an on-label prescription were 57 [63.3%]. Patients treated with an off-label drug had a significantly higher risk of adverse drug reactions [7.3% vs. 1.2%; p <0.01]. Conclusion: The present study indicates that children admitted to neonatal intensive care units are likely to receive an off-label medication; children who receive an off-label medication are usually more likely to be treated with more medication than the others; adverse drug reactions occur in patients admitted in neonatal intensive care and pediatrics are units are more frequently with off-label than with on-label drugs.

Objective: We present an interesting case of accidental overdose of latanoprost eye drops. Case Report: A 71-year-old patient underwent an uncomplicated cataract surgery in his right eye. During the first postsurgical week he mistakenly used latanoprost eye drops six times daily instead of the prescribed tobramycin/dexamethasone eye drops. The patient experienced gradually decreasing visual acuity and was diagnosed with cystoid macular edema seven weeks after surgery. The cystoid macular edema resolved 4 weeks later after treatment with nepafenac 0.3% eye drops and oral acetazolamide. The cystoid macular edema recurred 2 weeks after rechallenge with latanoprost. The rechallenge-induced cystoid macular edema once again resolved after cessation of latanoprost and retreatment with nepafenac eye drops. A Naranjo assessment score of 7 was obtained, indicating a probable relationship between the patient's symptoms and the suspect drug.

Introduction: Cycloserine and Kanamycin are approved for treatment of multidrug-resistant tuberculosis with good tolerability in Tuberculosis patients and have various labeled adverse reactions but the neuropsychiatric adverse drug reactions with cycloserine are rarely explained. Case Report: We present a case report on Cycloserine induced Suicidal tendencies and Kanamycin induced decrease in hearing sensation in Indian MDR-TB patient. A 55-year-old male patient who was diagnosed with MDR-TB was prescribed with category IV anti-tubercular therapy. Within one month of initiation of therapy, he developed repeated suicidal thoughts, joint pain, restlessness, depression, constipation, insomnia, tinnitus and a decrease in hearing sensation. Results and Discussion: Cycloserine and kanamycin were closely associated with suicidal tendency and tinnitus followed by a decrease in hearing sensations respectively. On causality assessment using WHO-UMC Causality assessment scale, Adverse Drug Reaction with Cycloserine was found to be certain and for kanamycin, ADR was found to be possible. Conclusion: Early management of such fatal ADR can improve the compliance, thus preventing the relapse of infection as well as improving therapeutic outcome in Tuberculosis patients.

Background: Elevations in serum Parathyroid Hormone (PTH) levels after denosumab administration have been described in medical literature among patients with renal impairment or intestinal malabsortion syndromes. Objective: To present a case of denosumab-induced normocalcemic hyperparathyroidism in a woman with postmenopausal osteoporosis without renal impairment or malabsorption syndrome. Case Report: A 62-year-old woman was diagnosed with postmenopausal osteoporosis (serum iPTH: 61pg/mL) and received anti-osteoporotic medication (70mg alendronate sodium once weekly and 1g/800IU calcium carbonate/cholecalciferol daily). Because of severe gastrointestinal symptoms, the alendronate sodium was discontinued and replaced it with denosumab 60mg/mL subcutaneously. Three months after first receiving denosumab, the serum iPTH, 25[OH]D and calcium levels were 1350pg/mL, 24.8ng/ml and 8.4mg/dL, respectively. This dramatic elevation of serum iPTH was attributed to receiving denosumab, as other causes of normocalcemic hyperparathyroidism were excluded. So, an interruption of denosumab for the second semester and reception only 2g/1600IU calcium carbonate/cholecalciferol daily was decided. Twelve months later the serum iPTH, 25[OH]D and calcium levels were 71pg/mL, 33.2ng/ml and 9.4mg/dL, respectively. Conclusion: A close monitoring of all patients prior to and during treatment with denosumab is suggested.

Background: Hyponatraemia is frequently encountered in clinical practice and is common among hospitalized patients. Tramadol is a commonly prescribed analgesia with a few adverse effects. However, on rare occasions, tramadol has been found to be associated with hyponatraemia. Case Report: In two patients described in this report, tramadol use was associated with symptomatic hyponatraemia which required hospitalization. Hyponatraemia was corrected after discontinuation of tramadol. A small number of patients with tramadol-associated hyponatraemia have been reported in the English-language medical literature. Hyponatraemia associated with tramadol is thought to be related to the syndrome of inappropriate antidiuretic hormone secretion. The association between tramadol and symptomatic hyponatraemia emphasizes the need to evaluate patients' electrolytes when they present with new symptoms after commencing on this drug.

Background: Ustekinumab is a fully human monoclonal antibody which binds Interleukin (IL)-12/23. It is indicated for the treatment of moderate-severe psoriasis and active psoriatic arthritis. Few data are available about the possibility of an interaction between ustekinumab and the liver. Case Description: We reported a case of a 61-year old woman admitted to our Unit for severe transaminase elevation (aspartate transaminase 756 IU/l, alanine transaminase 1212 IU/l) occurred after a single Ustekinumab infusion for psoriasis. All other possible causes of liver damage, including drugs, hepatitis viruses, auto-antibodies and metabolic disorders were excluded. Liver biopsy showed lymphocytic infiltration, biliary duct damage and piecemeal necrosis. On the bases of the nonspecific histological picture and Rucam score, we accomplished the diagnosis of “liver injury of iatrogenic origin”. After drug withdrawal, a spontaneous normalization of liver enzymes occurred within six months.

Background: Aceclofenac is a phenylacetic acid derivative belongs to the group of nonsteroidal anti-inflammatory drug. It is commonly used in the treatment of pain and various inflammatory disorders. It is well tolerated, with most adverse events being minor and reversible and affecting mainly the GI system. Case Report: Here, we report a rare occurrence of non-pigmenting fixed drug eruption after the use of aceclofenac in a 19 year old female.