12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/03/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/03/13

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/03/13

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Adverse Drug Events Associated with Low-Dose (10 mg) Versus High-Dose (25 mg) Empagliflozin in Patients Treated for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Diabetes Ther. 2018 Mar 09;:

Authors: Dai X, Luo ZC, Zhai L, Zhao WP, Huang F

Abstract
INTRODUCTION: Empagliflozin is a new, emerging oral hypoglycemic agent (OHA) which has shown significant benefits in type 2 diabetes mellitus (T2DM) patients with cardiovascular disease. In this analysis, our aim was to systematically compare the adverse drug events (ADEs) associated with a low (10 mg) versus a high (25 mg) dose of empagliflozin as (1) monotherapy, (2) as an add-on to other OHAs, and (3) as an add-on specifically to metformin, in patients who were treated for T2DM.
METHODS: This was a systematic review and meta-analysis of randomized controlled trials that compared empagliflozin 10 mg versus 25 mg in patients who were treated for T2DM and which reported adverse drug reactions as their clinical endpoints. Statistical analysis was carried out using the latest version of the RevMan software (ver. 5.3) whereby odds ratios (OR) and 95% confidence intervals (CI) were generated.
RESULTS: Eight trials with a total number of 8514 patients treated for T2DM were included in this meta-analysis and systematic review, of whom 4261 patients received 10 mg empagliflozin and 4253 patients received 25 mg empagliflozin. Our results showed that there were no significant differences between the patients with T2DM receiving 10 empagliflozin and those receiving 25 mg empagliflozin in terms of drug-related adverse effects (OR 1.06, 95% CI 0.93-1.21; P = 0.40, I2 = 0%), adverse events leading to drug discontinuation (OR 0.99, 95% CI 0.86-1.14; P = 0.87, I2 = 0%), and serious adverse events (OR 1.06, 95% CI 0.95-1.18; P = 0.31, I2 = 0%) when empagliflozin was provided as monotherapy or as an add-on to other anti-diabetic medications. The same results were obtained when empagliflozin was used as an add-on to metformin or as monotherapy. The duration of the follow-up periods did not affect the results. However, the incidence of genital and urinary tract infections (UTIs) was significantly higher in female patients than in male patients with 10 or 25 mg empagliflozin.
CONCLUSIONS: The incidence of ADEs was not significantly different in T2DM patients receiving 10 versus 25 mg empagliflozin as monotherapy or as add-on to metformin or other anti-diabetic drugs during a shorter or longer follow-up period. However, genital and UTIs were more common in female patients with T2DM irrespective of empagliflozin dosage.

PMID: 29524188 [PubMed - as supplied by publisher]

Selenium - a fascinating antioxidant of protective properties.

Adv Clin Exp Med. 2018 Feb;27(2):245-255

Authors: Kiełczykowska M, Kocot J, Paździor M, Musik I

Abstract
Selenium is a trace element which fulfils important functions in the organism. Its deficit may cause acute disorders, but an overdose can also lead to severe consequences. The functions of selenium in the organism are mainly connected with its antioxidant properties, as it is an essential part of important antioxidant enzymes. Disturbances of oxidant balance have been found to be involved in the activity of numerous harmful factors as well as in the pathogenesis of diverse illnesses. Selenium administration has proved to be effective against the toxicity of many agents and the side effects of drugs. However, the narrow range between therapeutic and toxic doses of selenium, as well as the dependence of its effect on the applied form, dose and method of treatment, makes the choice of the most effective supplement a very complex issue. Divergent forms of selenium are still being studied, including both inorganic and organic compounds as well as Se-enriched natural products. The newest research has also involved selenium nanoparticles. The aim of this review is to present the great potential of selenium for protecting the organism against a wide variety of environmental pollutants, drugs and physical factors.

PMID: 29521069 [PubMed - in process]

Recurrent dysphasia due to nivolumab-induced encephalopathy with presence of Hu autoantibody.

Lung Cancer. 2017 Jul;109:74-77

Authors: Raskin J, Masrori P, Cant A, Snoeckx A, Hiddinga B, Kohl S, Janssens A, Cras P, Van Meerbeeck JP

Abstract
A 58-year-old man was being treated for squamous non-small-cell lung cancer with nivolumab. At the 17th of biweekly administrations he presented with global dysphasia, dysarthria and myoclonus in the right upper extremity. MRI showed multiple T2/FLAIR hyperintense lesions in the left hemisphere; lumbar puncture showed lymphocytic pleiocytosis in the CSF without identifiable pathogens. Hu antibodies were present in serum and CSF. Nivolumab was discontinued and corticosteroids were administered. The neurological symptoms gradually improved; MRI showed complete remission of cerebral lesions. After rechallenge with nivolumab his symptoms and cerebral lesions recurred, proving the causal relationship with nivolumab. After tapering of corticosteroids, a second relapse occurred.

PMID: 28577954 [PubMed - indexed for MEDLINE]

Vitiligo in a patient with lung adenocarcinoma treated with nivolumab: A case report.

Lung Cancer. 2017 Jul;109:42-44

Authors: Uenami T, Hosono Y, Ishijima M, Kanazu M, Akazawa Y, Yano Y, Mori M, Yamaguchi T, Yokota S

Abstract
Nivolumab, an anti-programmed cell death-1 protein monoclonal antibody, is effective for treating patients with late-stage non-small-cell lung cancer. Immune checkpoint inhibitors such as nivolumab induce various kinds of immune-related adverse events, including vitiligo. Vitiligo has been reported in patients with melanoma but not lung cancer. We describe a 75-year-old man with lung adenocarcinoma, stage 4 with pleural and pericardial effusion, that progressed after first-line chemotherapy. Subsequently, he was treated with nivolumab as second-line therapy. After 6days of administering nivolumab, he developed vitiligo suddenly on the trunk of his body. Except for vitiligo, his physical examination was normal, and treatment with nivolumab was well tolerated. Therefore, this treatment was continued without further development or expansion of vitiligo. A computed tomography scan showed a reduction in the size of the lung nodule and stabilization of the pleural and pericardial effusion. This is the first case of vitiligo associated with the use of nivolumab in a patient with lung adenocarcinoma.

PMID: 28577948 [PubMed - indexed for MEDLINE]

Venous thromboembolism in hospitalized patients receiving chemotherapy for malignancies at Japanese community hospital: prospective observational study.

BMC Cancer. 2017 May 19;17(1):351

Authors: Kitayama H, Kondo T, Sugiyama J, Kurimoto K, Nishino Y, Hirayama M, Tsuji Y

Abstract
BACKGROUND: Although Asian population was recognized to have a lower risk of venous thromboembolism (VTE), its increasing prevalence and incidence remain unclear in patients with malignancies. We attempted to predict VTE development using activation markers of coagulation and fibrinolysis.
METHODS: We enrolled patients with malignancy admitted to Tonan Hospital between April and December 2014 to receive a new-for-them chemotherapy regimen. All patients were examined for VTE by computed tomography and whole-leg compression ultrasonography before chemotherapy and three months later. We also examined plasma levels of thrombin-antithrombin complex (TAT) and plasmin α2-plasmin inhibitor complex (PIC) before chemotherapy. The cut off values of TAT and PIC were set at 2.1 ng/mL and 1.8 μg/mL, respectively.
RESULTS: Of 97 patients, the majority (67%) had distant metastases. The most common malignancies were colorectal (26%), breast (23%), and stomach (19%) cancer. VTE was detected in 29 patients (31%); all were asymptomatic. VTE was newly developed in 12 patients in the three-month observation period, which means the incidence was 49 per 1000 person-years. Non-increased PIC with increased TAT was the only significant risk factor for both VTE prevalence and incidence in multivariate analysis, and the odds ratios were 3.0 (95% confidence interval, 1.1-8.2; P = 0.034) and 9.4 (95% confidence interval, 1.7-51.9; P = 0.011), respectively.
CONCLUSIONS: The prevalence and incidence of VTE were high in hospitalized Japanese patients receiving chemotherapy for malignancies. Non-increased PIC with increased levels of TAT may be an independent risk factor for VTE development.

PMID: 28525975 [PubMed - indexed for MEDLINE]

Exploring consumer opinions on the presentation of side-effects information in Australian Consumer Medicine Information leaflets.

Health Expect. 2016 Jun;19(3):543-56

Authors: Tong V, Raynor DK, Blalock SJ, Aslani P

Abstract
BACKGROUND: Consumer Medicine Information (CMI) is a brand-specific and standardized source of written medicine information available in Australia for all prescription medicines. Side-effect information is poorly presented in CMI and may not adequately address consumer information needs.
OBJECTIVE: To explore consumer opinions on (i) the presentation of side-effect information in existing Australian CMI leaflets and alternative study-designed CMIs and (ii) side-effect risk information and its impact on treatment decision making.
DESIGN: Fuzzy trace, affect heuristic, frequency hypothesis and cognitive-experiential theories were applied when revising existing CMI side-effects sections. Together with good information design, functional linguistics and medicine information expertise, alternative ramipril and clopidogrel CMI versions were proposed. Focus groups were then conducted to address the study objectives.
PARTICIPANTS AND SETTING: Three focus groups (n = 18) were conducted in Sydney, Australia. Mean consumer age was 58 years (range 50-65 years), with equal number of males and females.
RESULTS: All consumers preferred the alternative CMIs developed as part of the study, with unequivocal preference for the side-effects presented in a simple tabular format, as it allowed quick and easy access to information. Consumer misunderstandings reflected literacy and numeracy issues inherent in consumer risk appraisal. Many preferred no numerical information and a large proportion preferred natural frequencies.
CONCLUSIONS: One single method of risk presentation in CMI is unable to cater for all consumers. Consumer misunderstandings are indicative of possible health literacy and numeracy factors that influence consumer risk appraisal, which should be explored further.

PMID: 24905668 [PubMed - indexed for MEDLINE]

Life-threatening drug interactions: what the physician needs to know.

Intern Med J. 2017 May;47(5):501-512

Authors: Day RO, Snowden L, McLachlan AJ

Abstract
Adverse drug-drug interactions are a significant cause of adverse events and outcomes. Their incidence is rising, with more patients taking more drugs, and newer, more precise but often more hazardous drugs becoming available. Despite considerable information, including computerised alerts about potential adverse drug-drug interactions, prescribers increasingly override alerts, possibly symptomatic of the immense problem of evaluating the risk of an interaction in a particular patient. Many reports emanate from small studies often of normal and young volunteers, entirely different from the real world where, more often, older patients with multiple health conditions are receiving many more than the two drugs identified in the drug interaction report. Focusing on those drug-drug interactions that are clinically relevant is necessary, and increasingly, tools and reliable sources of this information are easily accessible.

PMID: 28503886 [PubMed - indexed for MEDLINE]

A decade of adverse drug events in Portuguese hospitals: space-time clustering and spatial variation in temporal trends.

BMC Pharmacol Toxicol. 2017 May 10;18(1):34

Authors: Scripcaru G, Mateus C, Nunes C

Abstract
BACKGROUND: The aim of this study is to identify the distribution by municipalities of adverse drug events (ADE) in Portugal, including adverse drug reactions (ADR) and accidental poisoning by drugs (AP), on municipality/years ADE rate clustering. Also we identify areas with different trends in time.
METHODS: We used a national dataset of public hospital discharges in Continental Portugal from 2004 to 2013. Events were identified based on codes: from E930 to E949.9 (ADR) and from E850 to E858.9 (AP). Space-time clustering and spatial variation in temporal trends methods were applied in three different time-periods: globally, by year and grouped in 2 classes (periods of 5 years).
RESULTS: A total of 9,320,076 patients were discharged within this period, with 133,688 patients (1.46%) having at least one ADE, 4% of them related with AP. Critical space-time identified clusters (p < 0.001) were the municipalities from Lisbon metropolitan area and Centro region area. The global rate increased at a 7.8% mean annual percentage change, with high space-time heterogeneity and variation in time trends clusters (p < 0.001). For whole period, 2004-2013, all clusters presented increasing trends. However when analyzed by period of 5 years we identified two clusters with decreasing trends in time in 2004-2008.
CONCLUSION: The impact of ADE is huge, with widely variations within country and in time, and represents an increasing challenge. Future research using individual and contextual risk factors are urgently needed to understand this spatiotemporal variability in order to promote local tailored and updated actions of prevention.

PMID: 28486949 [PubMed - indexed for MEDLINE]

A Bayesian analysis of quantal bioassay experiments incorporating historical controls via Bayes factors.

Stat Med. 2017 May 30;36(12):1907-1923

Authors: León Novelo LG, Womack A, Zhu H, Wu X

Abstract
This paper addresses model-based Bayesian inference in the analysis of data arising from bioassay experiments. In such experiments, increasing doses of a chemical substance are given to treatment groups (usually rats or mice) for a fixed period of time (usually 2 years). The goal of such an experiment is to determine whether an increased dosage of the chemical is associated with increased probability of an adverse effect (usually presence of adenoma or carcinoma). The data consists of dosage, survival time, and the occurrence of the adverse event for each unit in the study. To determine whether such relationship exists, this paper proposes using Bayes factors to compare two probit models, the model that assumes increasing dose effects and the model that assumes no dose effect. These models account for the survival time of each unit through a Poly-k type correction. In order to increase statistical power, the proposed approach allows the incorporation of information from control groups from previous studies. The proposed method is able to handle data with very few occurrences of the adverse event. The proposed method is compared with a variation of the Peddada test via simulation and is shown to have higher power. We demonstrate the method by applying it to the two bioassay experiment datasets previously analyzed by other authors. Copyright © 2017 John Wiley & Sons, Ltd.

PMID: 28106916 [PubMed - indexed for MEDLINE]

Long-term (52-week) safety and efficacy of Sacubitril/valsartan in Asian patients with hypertension.

Hypertens Res. 2017 May;40(5):472-476

Authors: Supasyndh O, Sun N, Kario K, Hafeez K, Zhang J

Abstract
Sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor-neprilysin inhibitor, demonstrated significant reductions in office and 24 h ambulatory blood pressure (BP) over 8 weeks in Asian patients with hypertension. This 52-week extension to the 8-week core study was aimed at evaluating the long-term safety, tolerability and efficacy of sacubitril/valsartan. Patients who completed an 8-week randomized study (the core study) were enrolled in this 52-week open-label study and received sacubitril/valsartan 200 mg QD. The sacubitril/valsartan dose was uptitrated to 400 mg QD if BP was uncontrolled (>140/90 mm Hg) after 4 weeks. Subsequently, in patients with uncontrolled BP, treatment was intensified every 4 weeks with amlodipine 5-10 mg followed by hydrochlorothiazide 6.25-25 mg. Of the 341 patients enrolled, 7 (2.1%) discontinued the study drug due to adverse events (AEs). The incidence of AEs and serious AEs were 63.9 and 3.8%, respectively, and no deaths were reported in this study. The most frequent AEs were nasopharyngitis (18.2%) and dizziness (8.8%). Events that were potentially indicative of low BP were infrequent. One patient reported mild transient angioedema (lasting 2.5 h) that resolved without treatment but led to study drug discontinuation. The sacubitril/valsartan-based regimen provided clinically significant mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (-24.7/-16.2 mm Hg). The overall BP control, msSBP and msDBP response rates were 75.3, 90.6 and 87.6%, respectively. Long-term use of sacubitril/valsartan was generally safe and well-tolerated in patients with hypertension and provided significant BP reductions from baseline.

PMID: 27853163 [PubMed - indexed for MEDLINE]

Assessment of Drug Therapy-Related Issues in an Outpatient Heart Failure Population and the Potential Impact of Pharmacist-Driven Intervention.

J Pharm Pract. 2017 Jun;30(3):318-323

Authors: Dempsey JT, Matta LS, Carter DM, Stevens CA, Stevenson LW, Desai AS, Cheng JW

Abstract
BACKGROUND: The Ambulatory Cardiac Triage, Intervention, and Education (ACTIVE) infusion unit is an outpatient center that aims to provide heart failure (HF) patients with comprehensive multidisciplinary interventions.
OBJECTIVE: To describe the patient population served in ACTIVE and to document the prevalence of comorbidities and drug therapy-related issues (DRIs) in order to define the most effective role of a pharmacist in the unit.
METHODS: Patients who have been interviewed by a pharmacist in ACTIVE were included. Comprehensive medical and medication profile reviews were performed. Patient comorbidities were documented, and DRIs were classified.
RESULTS: Sixty patients were included. Most prevalent cardiac comorbidities included hypertension (73%) and hyperlipidemia (62%). Top 3 noncardiac comorbidities included chronic kidney disease (60%), diabetes (50%), and obesity (35%). The prevalence of DRI was reported as follows: (1) needs additional/alternative therapy (untreated indication [37] or suboptimal therapeutic choice [46]), (2) wrong drug (major drug-drug interaction [90], contraindication [11], or duplicate therapy [1]), (3) suboptimal dosing (17), (4) dose exceeds recommended maximum (9), and (5) adverse drug reaction (93). In 63 (22%) of the DRIs, a pharmacist made recommendations to modify the regimen.
CONCLUSION: The prevalence of DRI is high even among HF patients managed in a subspecialty cardiovascular practice. Pharmacists in this setting play a vital role in more effectively resolving DRI.

PMID: 27080398 [PubMed - indexed for MEDLINE]

Does low-dose methotrexate deserve more respect from clinicians?

JAAPA. 2017 May;30(5):12-15

Authors: Luu B, Rodway GW

Abstract
Medical errors associated with low-dose methotrexate may be life-threatening. Prescribers should be cognizant of the medication's toxicities and the persistent challenges in preventing adverse events. This article reviews the properties of methotrexate and its common drug-drug interactions. Best practices from the Institute for Safe Medication Practices, aimed at reducing methotrexate errors, are highlighted.

PMID: 28441215 [PubMed - indexed for MEDLINE]

Drug-associated pulmonary arterial hypertension.

Clin Toxicol (Phila). 2018 Mar 06;:1-9

Authors: McGee M, Whitehead N, Martin J, Collins N

Abstract
INTRODUCTION: While pulmonary arterial hypertension remains an uncommon diagnosis, various therapeutic agents are recognized as important associations. These agents are typically categorized into "definite", "likely", "possible", or "unlikely" to cause pulmonary arterial hypertension, based on the strength of evidence.
OBJECTIVE: This review will focus on those therapeutic agents where there is sufficient literature to adequately comment on the role of the agent in the pathogenesis of pulmonary arterial hypertension.
METHODS: A systematic search was conducted using PubMed covering the period September 1970- 2017. The search term utilized was "drug induced pulmonary hypertension". This resulted in the identification of 853 peer-reviewed articles including case reports. Each paper was then reviewed by the authors for its relevance. The majority of these papers (599) were excluded as they related to systemic hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus, pulmonary fibrosis, alternate differential diagnosis, treatment, basic science, adverse effects of treatment, and pulmonary hypertension secondary to pulmonary embolism. Agents affecting serotonin metabolism (and related anorexigens): Anorexigens, such as aminorex, fenfluramine, benfluorex, phenylpropanolamine, and dexfenfluramine were the first class of medications recognized to cause pulmonary arterial hypertension. Although most of these medications have now been withdrawn worldwide, they remain important not only from a historical perspective, but because their impact on serotonin metabolism remains relevant. Selective serotonin reuptake inhibitors, tryptophan, and lithium, which affect serotonin metabolism, have also been implicated in the development of pulmonary arterial hypertension. Interferon and related medications: Interferon alfa and sofosbuvir have been linked to the development of pulmonary arterial hypertension in patients with other risk factors, such as human immunodeficiency virus co-infection. Antiviral therapies: Sofosbuvir has been associated with two cases of pulmonary artery hypertension in patients with multiple risk factors for its development. Its role in pathogenesis remains unclear. Small molecule tyrosine kinase inhibitors: Small molecule tyrosine kinase inhibitors represent a relatively new class of medications. Of these dasatinib has the strongest evidence in drug-induced pulmonary arterial hypertension, considered a recognized cause. Nilotinib, ponatinib, carfilzomib, and ruxolitinib are newer agents, which paradoxically have been linked to both cause and treatment for pulmonary arterial hypertension. Monoclonal antibodies and immune regulating medications: Several case reports have linked some monoclonal antibodies and immune modulating therapies to pulmonary arterial hypertension. There are no large series documenting an increased prevalence of pulmonary arterial hypertension complicating these agents; nonetheless, trastuzumab emtansine, rituximab, bevacizumab, cyclosporine, and leflunomide have all been implicated in case reports. Opioids and substances of abuse: Buprenorphine and cocaine have been identified as potential causes of pulmonary arterial hypertension. The mechanism by which this occurs is unclear. Tramadol has been demonstrated to cause severe, transient, and reversible pulmonary hypertension. Chemotherapeutic agents: Alkylating and alkylating-like agents, such as bleomycin, cyclophosphamide, and mitomycin have increased the risk of pulmonary veno-occlusive disease, which may be clinically indistinct from pulmonary arterial hypertension. Thalidomide and paclitaxel have also been implicated as potential causes. Miscellaneous medications: Protamine appears to be able to cause acute, reversible pulmonary hypertension when bound to heparin. Amiodarone is also capable of causing pulmonary hypertension by way of recognized side effects.
CONCLUSIONS: Pulmonary arterial hypertension remains a rare diagnosis, with drug-induced causes even more uncommon, accounting for only 10.5% of cases in large registry series. Despite several agents being implicated in the development of PAH, the supportive evidence is typically limited, based on case series and observational data. Furthermore, even in the drugs with relatively strong associations, factors that predispose an individual to PAH have yet to be elucidated.

PMID: 29508628 [PubMed - as supplied by publisher]

Integration of genome-scale metabolic networks into whole-body PBPK models shows phenotype-specific cases of drug-induced metabolic perturbation.

NPJ Syst Biol Appl. 2018;4:10

Authors: Cordes H, Thiel C, Baier V, Blank LM, Kuepfer L

Abstract
Drug-induced perturbations of the endogenous metabolic network are a potential root cause of cellular toxicity. A mechanistic understanding of such unwanted side effects during drug therapy is therefore vital for patient safety. The comprehensive assessment of such drug-induced injuries requires the simultaneous consideration of both drug exposure at the whole-body and resulting biochemical responses at the cellular level. We here present a computational multi-scale workflow that combines whole-body physiologically based pharmacokinetic (PBPK) models and organ-specific genome-scale metabolic network (GSMN) models through shared reactions of the xenobiotic metabolism. The applicability of the proposed workflow is illustrated for isoniazid, a first-line antibacterial agent against Mycobacterium tuberculosis, which is known to cause idiosyncratic drug-induced liver injuries (DILI). We combined GSMN models of a human liver with N-acetyl transferase 2 (NAT2)-phenotype-specific PBPK models of isoniazid. The combined PBPK-GSMN models quantitatively describe isoniazid pharmacokinetics, as well as intracellular responses, and changes in the exometabolome in a human liver following isoniazid administration. Notably, intracellular and extracellular responses identified with the PBPK-GSMN models are in line with experimental and clinical findings. Moreover, the drug-induced metabolic perturbations are distributed and attenuated in the metabolic network in a phenotype-dependent manner. Our simulation results show that a simultaneous consideration of both drug pharmacokinetics at the whole-body and metabolism at the cellular level is mandatory to explain drug-induced injuries at the patient level. The proposed workflow extends our mechanistic understanding of the biochemistry underlying adverse events and may be used to prevent drug-induced injuries in the future.

PMID: 29507756 [PubMed]

New low-dose liquid pilocarpine formulation for treating dry mouth in Sjögren's syndrome: clinical efficacy, symptom relief, and improvement in quality of life.

J Pharm Health Care Sci. 2018;4:4

Authors: Watanabe M, Yamada C, Komagata Y, Kikuchi H, Hosono H, Itagaki F

Abstract
Background: Patients with Sjögren's syndrome (SS) typically present clinically with xerostomia (dry mouth) because of progressive damage to the exocrine glands. We developed a new, low-dose pilocarpine/sodium alginate (LPA) solution with pilocarpine hydrochloride to inhibit systemic adverse effects by administering via the oral mucosa. The purpose of this study was to assess its stability, safety, and efficacy.
Methods: The pilocarpine concentration in an LPA liquid formulation was measured 3, 7, 14, and 28 days after preparation to assess its stability. A prospective clinical trial was undertaken to assess the efficacy and safety of the LPA solution as a symptomatic treatment for dry mouth in SS. Patients (n = 24) with clinically significant xerostomia were enrolled after providing written informed consent. Whole-mouth salivary flow rate was measured twice; immediately before and 60 min after LPA application. Symptoms were assessed by questionnaire with visual analog scales or checkboxes before the first application (baseline), and then once daily for 7 days.
Results: The pilocarpine content 3, 7, 14, and 28 days after preparation showed no marked change, confirming its stability. Salivary flow was significantly increased from 0.076 ± 0.092 g/30 s to 0.122 ± 0.140 g/30 s 60 min after LPA administration (P < 0.001). Dry mouth and thirstiness showed significant improvement compared with that of baseline (P ≤ 0.01). The only adverse effect was sweating, and no serious drug-related adverse events were reported.
Conclusions: This new, low-dose pilocarpine formulation was well-tolerated and resulted in significant improvements in symptoms of dry mouth and other xerostomic conditions in patients with SS.
Trial registration: The study approval number in the institution; 08-068-2. Registered January 19, 2009. UMIN000029307. Registered 27 September 2017 (retrospectively registered).

PMID: 29507747 [PubMed]

Analysis of Adverse Drug Reaction Risk in Elderly Patients Using the Japanese Adverse Drug Event Report (JADER) Database.

Biol Pharm Bull. 2017;40(6):824-829

Authors: Chisaki Y, Aoji S, Yano Y

Abstract
In general, the risk of adverse drug reactions (ADRs) is higher in elderly patients than in younger patients. In this study, we performed a comprehensive assessment of the risks of possible drug-ADR combinations in elderly patients using the Japanese Adverse Drug Event Report (JADER) database of the Pharmaceutical and Medical Devices Agency (PMDA, Japan) using the reporting odds ratio (ROR) as an index. Data recorded from April 2004 to September 2015 in the JADER database were downloaded from the PMDA website. The patients were classified into younger (≤69 years old) and elderly (≥70 years old) groups. The ROR and 95% confidence interval (CI) were calculated for all combinations of drugs and ADRs for which there were three or more reports in the database, focusing particularly on the combinations where more than 100 cases had been reported in elderly and younger patients. The most frequently reported drug-ADR combination was methotrexate with interstitial lung disease (646 cases). The combination with the highest ROR was methotrexate with lymphoproliferative disorder (ROR: 484.6, 95% CI: 334.1-702.9). In total, 27 drug-ADR combinations were found to have high risk in elderly patients. In conclusion, the findings of this comprehensive assessment of drug-ADR combinations using the JADER database will be valuable for updating the ADR risks for elderly patients in clinical setting.

PMID: 28566626 [PubMed - indexed for MEDLINE]

Adverse effects of levamisole in cocaine users: a review and risk assessment.

Arch Toxicol. 2017 Jun;91(6):2303-2313

Authors: Brunt TM, van den Berg J, Pennings E, Venhuis B

Abstract
The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils. A large proportion of cases also involved vasculopathy, characterized by pronounced black and purple skin purpura with cutaneous necrosis. Females are more susceptible for both agranulocytosis and vasculitis. Another complication reported with levamisole-adulterated cocaine is leukoencephalopathy, a disabling and potentially fatal neurological disorder caused by cerebral demyelination. In this review, all adverse effects associated with therapeutic levamisole and levamisole-adulterated cocaine are described. In addition, this review provides an update of the pharmacology of levamisole, its metabolism, including toxic metabolites and metabolites that are relevant for levamisole's addition to cocaine. Special emphasis is put on the immunopathology and the dose-effect relationship of chronic levamisole exposure. Finally, a risk assessment is provided based on the current level of levamisole adulteration in street cocaine, the dose range calculated per gram and the pattern of chronic exposure in heavy or dependent users.

PMID: 28314885 [PubMed - indexed for MEDLINE]