Current Drug Safety - Volume 14, Issue 2, 2019

Background: Recently, Food and Drug Administration (FDA) has approved sodium/ glucose co-transporter 2 (SGLT2) inhibitors for the treatment of diabetes mellitus. However, regarding adverse drug reactions (ADRs) of SGLT2 inhibitors in large group of population, very less information is available. Thus, we have tried to find out the risk profile of SGLT2 inhibitors. Materials and Methods: A total of 1,042 studies have been published from Nov. 2012-Nov. 2017 regarding SGLT2 inhibitors. After inclusion and exclusion criteria, 27 studies have been selected for the analysis of risk. Results and Discussion: The emerging evidence indicates various adverse drug reactions such as foot and toe amputation, cancer, diabetic ketoacidosis, bone fracture risk and urinary as well as mycotic genital infection. The causality assessment has shown a correlation between SGLT2 inhibitors and diabetic ketoacidosis and urinary tract infection. Conclusion: In conclusion, Marketing Authorization Holder (MAH) and Regulatory Authorities (RA) should monitor various adverse drug reactions such as diabetic ketoacidosis and urinary tract infection with the use of SGLT2 inhibitor.

Background: Idiosyncratic Drug Induced Liver Injury (DILI) is a rare adverse event to drugs that occasionally leads to severe liver damage, being one of the leading causes of Acute Liver Failure (ALF) in developed countries. DILI is largely a diagnosis of exclusion. Discussion and Conclusion: Careful history of drug taking and ruling out other competing etiologies is mandatory given that DILI can present with an extremely variable phenotype. Several prognostic scores have been developed to promptly identify patients with potential risk of developing ALF. New biomarkers to diagnose and predict DILI evolution are under study and hopefully we will benefit from these novel tools in the near future.

Background: Hypertensive disorders of pregnancy including gestational hypertension, preeclampsia and eclampsia are conditions that cause significant perinatal and maternal morbidity and mortality. Objective: This is a systematic review of the current evidence examining the relationship between both depression and antidepressants on pregnancy-related hypertensive conditions. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, six databases were searched for articles published between January 1990 and December 2017 (PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, MEDLINE and ClinicalTrials. gov). Randomized control trials, cohort studies and case-control studies were included in this review. Studies that measured the following exposures were included: Antidepressant exposure or diagnosis of depression. Studies that measured the following outcomes were included: Gestational hypertension, preeclampsia or eclampsia. A combination of keywords, as well as Medical Subject Headings (MeSH) index terms, was used for three general categories: antidepressants, depression and hypertensive disorders of pregnancy. A total of 743 studies were identified and 711 were excluded based on relevance to the research question. Twenty studies were included in the final systematic review. Results: Of the twenty relevant studies, ten specifically examined the relationship between depression and hypertension in pregnancy. Only two of these did not find a significant association. Of the ten studies that concentrated on antidepressant medications, all except one found an association with hypertension in pregnancy to varying degrees. Conclusion: Review of the literature suggests a possible association between depression and antihypertensive medications with pregnancy-related hypertension, but further studies are needed.

Background: Some studies have linked the use of paracetamol (PAR) with adverse effects like wheezing, exacerbation of asthma symptoms and other respiratory problems. Other studies are inconclusive or deny this correlation. This makes the association between PAR and airway hypersensitivity very controversial and still under debate. Objective: This work investigated if chronic treatment with PAR in rats could directly affect the contraction and relaxation for different stimulus in isolated airways. Methods: Rats were treated for 2 weeks with PAR (400 mg/Kg, v.o.). The blood was collected for biochemical analysis (alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBARs reaction and glutathione) and isolated tracheal rings were prepared in organ bath to measure isometric tone after contractile and relaxant stimulus. Results: Hepatic enzymes (ALT, AST) and lipid peroxidation were increased after PAR-treatment, while glutathione was decreased. Rats do not present any alteration in airway myocytes responsiveness, either to contractile or relaxant stimulus (i.e. cholinergic agonist, membrane depolarization, Ca2+ influx across sarcolemma, internal Ca2+ release from sarcoplasmic reticulum, Ca2+ channel blocking, β-agonist and NOmediating relaxation). Conclusion: Despite increased oxidative stress and reduced antioxidant defense, chronic treatment with PAR does not induce airway hypersensitivity or risk of asthma in rats.

Background: Advances in the clinical management of diseases have been accompanied by increasing complexity of treatment regimens. The complexity of medication regimen is of concern for patients as well as doctors as it may adversely affect patient compliance and treatment outcomes. It may result in medication errors, increased utilization of health resources owing to a reduction in treatment effectiveness, and increased risk of therapeutic failure. Objective: This study aimed to assess the complexity of medication regimen prescribed to patients on hospital discharge using the medication regimen complexity index (MRCI). Methods: A cross-sectional, descriptive study was conducted. Hospital discharge prescriptions written for patients discharged from the General Medicine wards of a tertiary care teaching hospital in South India were scored for their complexity using MRCI. The correlation of age and gender with the MRCI scores was also assessed. Patients ≥60 years of age were considered elderly. Results: The median MRCI score for 563 prescriptions studied was 14 (Interquartile range, 9−21). Elderly patients received a significantly more complex medication regimen compared with younger patients (p < 0.001) at the time of hospital discharge. Gender variation was seen with higher MRCI scores in females, but this was not statistically significant in the elderly group. Conclusion: MRCI scores are significantly high in elderly patients at the time of hospital discharge. Although a strong correlation is seen between the number of medications and the MRCI score, the latter helps to distinguish regimen complexity between prescriptions with the same number of medications.

Background: Radiocontrast media are used extensively nowadays to visualize internal organs. Currently, non-ionic iodinated contrast media are used which are generally considered to be safe but some adverse reactions have been reported. Thus, the present study was carried out to analyze the nature and incidence of adverse drug reactions (ADRs) to radiographic contrast media in a teaching hospital. Methods: An observational study carried out for a period of six months in a teaching hospital. Contrast media induced adverse reactions were analyzed in terms of affected organs, rate, causality assessment, severity and preventability. The treatment and outcomes of adverse events were also recorded. Naranjo Probability Scale was used to evaluate the relationship between the contrast agent used and the suspected ADR. The severity of the suspected ADRs was determined using Hartwig Scale and preventability was assessed using modified Schumock and Thornton criterion. Results: A total of 15 suspected ADRs occurred in 11 patients with an incidence of 1.4%. It included 5 (45.4%) males and 6 (54.5%) females (p < 05). The highest percentage (72.7 %) of ADRs was seen in adult patients, the mean age being 40.8 years. Vomiting (33.3%) was the most common ADR noted followed by severe nausea and rashes. 64.7 % of ADRs were categorized as probable and 35.3 % were possible. Adverse reactions required treatment in 46.6% patients. There was no fatality reported. Conclusion: The reactions observed were mild to moderate in severity and occurred within 30 minutes of the administration of the contrast.

Background: Several botanical species are poisonous and are used for medicinal purposes in traditional medicine. In fact, a relationship between toxicity and phytotherapeutic potential of medicinal plants exists. Objective: Until now, there is no ethnopharmacological indices evaluating mathematically the toxic property of any medicinal plant used traditionally. Consequently, it is important to find this link through the establishment and development of novel indices that put into consideration the relationship between toxicity and phytotherapy. Two essential objectives were targeted in the present investigation: firstly, we aimed to establish novel indices which permit researchers to evaluate data obtained in any ethnobotanical survey targeting toxic plants. Secondly, we aimed also to collect data and information about toxic species, mainly those used traditionally for therapeutic purposes in the region of Tafilalet (southeast of Morocco). Methods: The total informant interviewed in our study was 1616 (where 1500 were simple local inhabitants and 116 were herbalists). This inquiry was carried out through semi-structured and structured interviews and the sampling technique used was the stratified sample (9 stratums). Data obtained was analyzed using 3 new indices: Degree of Taxonomic Toxicity (DT), Degree of Botanical Families Toxicity (DFT) and Relative Link of Toxicity (RLT). Results: 47 toxic species belonging to 38 botanical families were quoted in our survey. The highest value of DT was observed for Atractylis gummifera L. (DT=24.67). According to the calculated value of DFT, the most toxic plant family in the region of Tafilalet was Asteraceae (DFT=143.90). Nervous system disorders are the main ailment caused by the toxicity of poisonous species used in the traditional medicine in Tafilalet (RLT=1.44). Conclusion: Novel indices established in this investigation (DT, DFT and RLT) have been demonstrated to be useful for interpreting data collected in Tafilalet region and could serve for other ethnopharmacological surveys of toxic medicinal plants.

Background: The objective of this survey was to describe the clinical monitoring practically used after intravenous, subcutaneous or neuraxial (epidural or intrathecal) administration of morphine. Methods: It was a descriptive, retrospective, multicenter (10 hospitals) survey based on the medical charts’ analysis, which evaluated the postoperative clinical monitoring after morphine administration. Results: Morphine was delivered intravenously (69%), intrathecally (19%), epidurally (10%) and/or subcutaneously (12%). Clinical monitoring protocols and protocols for the management of side effects were both present in 60% (n=6/10), only one of the two types of protocols in 10% (n=1/10) and both absent in 30% (n=3/10). Protocols for the management of respiratory depression and consciousness evaluation were present in 70% of cases (n=7/10). These events were reported on medical records without any prescription or protocol in 35% (n=14/40) and 37,5% (n=15/40) respectively. Prescriptions for respiratory rate evaluation and clinical monitoring of consciousness were in agreement with only 20% of the medical data and medical records. Different levels of respiratory rate were observed: 43% (n=3/7) below 8/min, 43% (n=3/7) below 10/min and 14% (n=1/7) below 12/min. Clinical monitoring was not performed in 31% (n=31/100) for consciousness and in 35% (n=35/100) for respiratory rate. Pulse oximeter was used in 48% (n=48/100) of patients. Capnography was never used. Respiratory depression occurred in 1% (n=1/100) of cases. Conclusion: This survey emphasizes an important disparity in the prescription of medical monitoring and a lack of use of protocols when morphine is administered. It demonstrates the need for a standardization of protocols according to the existing guidelines.

Background: Either direct or indirect tumor necrosis factor (TNF)-alpha blockers are usually used to treat psoriatic arthritis (PA), but their use can increase susceptibility to infectious diseases. Case Presentation: We report a rare case of double skin-knee wound and lung non-tubercular infection in a patient with PA under TNF-alpha blockers therapy. About 1 year after the beginning of adalimumab, a 48-year-old smoker suffering of PA was hospitalized for the skin-knee wound. Results: Clinical evaluation and biochemical markers excluded the presence of a systemic disease, and a skin infection sustained by leishmaniasis probably related to adalimumab was diagnosed (Naranjo score: 6). Adalimumab was discontinued and oral treatment with apremilast and topical treatment with meglumine antimoniate was started with a complete remission of skin wound in 2 weeks. About 7 months later when the patient was under apremilast treatment, he presented to our observation for dyspnea, cough and fever. High-Resolution Computer Tomography (HRCT) chest highlighted alveolar involvement with centrilobular small nodules, branching linear and nodular opacities. Microbiological culture of both broncho-alveolar lavage fluid and sputum documented an infection sustained by nontuberculous mycobacteria. Even if apremilast treatment probably-induced lung infection, we can’t exclude that it worsened a clinical condition induced by adalimumab. Apremilast was stopped and an empirical antitubercular treatment was started. Patient's breathlessness and cough improved as confirmed also by HRCT chest. Conclusion: This case highlights the importance to consider the possibility to develop leishmaniasis and/or non-tubercular mycobacterial infection in patients treated with TNF-alpha inhibitors.

Introduction: Imatinib is the treatment of choice in patients with locally advanced or metastatic gastrointestinal stromal tumours (GIST). Clinical tolerance of imatinib is excellent except for the common adverse drug reaction (ADR). Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a severe, potentially life-threatening drug-induced hypersensitivity reaction, characterized by cutaneous eruptions, fever, diffuse lymphadenopathy, along with eosinophilia, and elevated liver function tests. This ADR is rarely reported with imatinib. Only four cases of DRESS syndrome associated with imatinib have already been published. Case Report: We report an exceptional case of DRESS syndrome associated with imatinib in a 46 year-old woman with GIST. Two weeks after she had started imatinib therapy, she developed a skin rash, with eosinophilia and elevated liver tests. Plasma level of imatinib was within the therapeutic range. Imatinib was immediately discontinued. A favourable outcome was slowly observed after the drug had been stopped. Results and Conclusion: This case was scored three according to the European Registry of Severe Cutaneous Adverse Reactions Study Group (RegiSCAR). The Naranjo score for imatinib was five (probable).

Background: Atypical antipsychotics, unlike traditional antipsychotics, are considered to have limited cardiovascular side effects, but recent evidence drew attention to potential cardiac rhythm disturbances during aripiprazole therapy. Prolonged QT-interval and increased heart rate were described during treatment with therapeutic doses of aripiprazole, and some reports have even shown relevant arrhythmias, such as ventricular trigeminy and supraventricular tachycardia, in patients treated with this drug. Case Report: Here, we report a case of a young female who attempted suicide with aripiprazole overdose presenting with a concomitant 2:1 second degree atrioventricular block. Little is known on the cardiac toxicity of atypical antipsychotics in overdose: reporting this case description, far from establishing direct causality. Results and Conclusion: We would promote further efforts to define the possible effects of the drug on the cardiac conduction system, for a safer management of patients in clinical practice.

Background: Drug hypersensitivity reactions to infliximab have been reported in pediatric patients. At times, these patients may need infliximab administration in spite of hypersensitivity. However, only a few reports of desensitization protocols are available in the literature in pediatric patients. Case Report: We report a case of immediate hypersensitivity reaction to intravenous infliximab in a 13-year-old child suffering from pustular psoriasis who eventually underwent a 14 step desensitization protocol for the administration of infliximab in a pediatric intensive care unit. Results and Conclusion: Although our desensitization protocol was safe and effective, we recommend the entire desensitization procedure to be performed under the supervision of experienced personnel in a pediatric intensive care unit. Future studies with larger sample size are needed to confirm our findings.

Background: Metronidazole, a widely used antibacterial and antiprotozoal drug, is often the drug of choice in amoebic liver abscess. The drug, otherwise safe, can cause serious central nervous disturbances in rare circumstances. Case Report: Here, we report a case of cerebellar dysfunction in the form of slurring of speech and episodes of falls, in an elderly male following a three-week course of metronidazole therapy. Results and Conclusion: The patient manifested classic radiologic features of metronidazole neurotoxicity. Marked improvement in clinical symptoms was seen following drug discontinuation.

Background: Selective Serotonin Reuptake Inhibitors (SSRIs) are the first-line treatments for various psychiatric disorders. SSRIs offer an improved side effect profile compared to older treatments, which improves patients’ adherence and quality of life. Case Report: Here we discuss a case of an uncommon, but a distressing side effect of citalopram. A 76-year old woman was referred to the psychiatry clinic for bizarre behavior. The patient was diagnosed with behavioral variant frontotemporal dementia and was started on citalopram 20 mg and aripiprazole 5 mg daily. At 3.5 months the patient complained of diffuse hair thinning on her scalp. Citalopram was considered the offending agent and was discontinued. Within a few months, the patient regained most of her hair. Although drug-induced alopecia is common among other SSRIs, it is relatively rare with citalopram. Results and Conclusion: Early recognition, withdrawal of offending agent, and reassurance to the patient that hair loss is reversible can help alleviate patient distress and avoid relapse.