Pharmacokinetics and safety of fidaxomicin in patients with inflammatory bowel disease and Clostridium difficile infection: an open-label Phase IIIb/IV study (PROFILE).

J Antimicrob Chemother. 2018 12 01;73(12):3430-3441

Authors: Högenauer C, Mahida Y, Stallmach A, Marteau P, Rydzewska G, Ivashkin V, Gargalianos-Kakolyris P, Michon I, Adomakoh N, Georgopali A, Tretter R, Karas A, Reinisch W

Abstract
Objectives: Inflammatory bowel disease (IBD) poses an increased risk for Clostridium difficile infection (CDI). Fidaxomicin has demonstrated non-inferiority to vancomycin for initial clinical cure of CDI in patients without IBD; however, lack of data has caused concerns regarding potential systemic absorption of fidaxomicin in patients with IBD.
Methods: The plasma pharmacokinetics (PK) of fidaxomicin and its primary metabolite OP-1118 were evaluated in a multicentre, open-label, single-arm, Phase IIIb/IV study enrolling patients with active IBD and CDI. Patients received fidaxomicin, 200 mg twice daily for 10 days. The primary and secondary endpoints were, respectively, plasma and stool PK of fidaxomicin and OP-1118 on Days 1, 5 and 10 of treatment. Other secondary endpoints included safety of fidaxomicin treatment (assessed until Day 180). ClinicalTrials.gov identifier: NCT02437591.
Results: Median Tmax of fidaxomicin and OP-1118 for the PK analysis set (PKAS; 24 patients) was 1-2 h across Days 1, 5 and 10. Cmax ranges were 1.2-154 ng/mL for fidaxomicin and 4.7-555 ng/mL for OP-1118 across Days 1, 5 and 10 (PKAS). The ranges of concentrations in stool were 17.8-2170 μg/g for fidaxomicin and 0-1940 μg/g for OP-1118. Sixty percent (15/25) of patients experienced treatment-emergent adverse events (TEAEs), none of which led to treatment discontinuation or death.
Conclusions: Maximum fidaxomicin and OP-1118 plasma concentrations observed in this study population suggest no increase in absorption, compared with patients without IBD. Incidence of TEAEs was similar to previous Phase III trials, suggesting that fidaxomicin is comparatively well tolerated in patients with IBD.

PMID: 30260412 [PubMed - indexed for MEDLINE]

Identifying signals of interest when screening for drug-outcome associations in health care data.

Br J Clin Pharmacol. 2018 09;84(9):1865-1867

Authors: Pottegård A, Hallas J, Wang SV, Gagne JJ

PMID: 29862551 [PubMed - indexed for MEDLINE]

Patient involvement is essential in identifying drug-related problems.

Br J Clin Pharmacol. 2018 09;84(9):2048-2058

Authors: Kari H, Kortejärvi H, Airaksinen M, Laaksonen R

Abstract
AIMS: The aim of this study is to evaluate how critical patient involvement is in pharmacist-led clinical medication reviews and in identifying the most significant clinical drug-related problems (DRPs).
METHODS: Pharmacist-led clinical medication reviews were conducted with 161 consenting patients aged ≥75 years with at least seven prescribed medicines, living independently at home in Finland. A pharmacist, a nurse and a physician evaluated the clinical significance of the DRPs identified during the patient interview at an interprofessional case conference. It was evaluated whether the most significant clinical DRPs could also have been identified through reviewing the medication list only or the medication list and certain patient details.
RESULTS: Altogether, the 111 most significant clinical DRPs were evaluated. Only 6% could have been identified through reviewing the medication list only, and 16% through reviewing the medication list and certain patient details. Hence, 84% of the most significant clinical DRPs could only have been identified with patient involvement. The most common DRPs were: poor therapy control (25%); nonoptimal drug (22%); intentional nonadherence (12%); and additional drug needed (11%). patient involvement was critical when identifying DRPs related to additional drug needed, unintentional nonadherence, use of over-the-counter medicines or dietary supplements, or contradictions in counselling.
CONCLUSION: Patient involvement is essential when identifying clinical DRPs. Indeed, poor therapy control, nonoptimal drug use, intentional or unintentional nonadherence might otherwise be missed.

PMID: 29774588 [PubMed - indexed for MEDLINE]

No differences in olanzapine- and risperidone-related weight gain between women and men: a meta-analysis of short- and middle-term treatment.

Acta Psychiatr Scand. 2018 08;138(2):110-122

Authors: Schoretsanitis G, Drukker M, Van Os J, Schruers KRJ, Bak M

Abstract
OBJECTIVE: A plethora of data deriving from single studies as well as meta-analyses demonstrates that weight gain is associated with the exposure to the majority of antipsychotics (AP). However, potential sex differences have widely evaded the attention of AP treatment trials. It is hypothesised that female patients gain more weight compared with male patients due to their enhanced susceptibility to adverse drug reactions.
METHOD: A meta-analysis was conducted using clinical trials of AP that reported weight change separately for female and male patients. Duration of AP use was stratified in four categories: <6 weeks, 6-16 weeks, 16-38 weeks and >38 weeks. Forest plots were generated for men and women separately, stratified by AP as well as by duration of use. Sex differences were tested by performing meta-regression.
RESULTS: Data of 26 studies were used in the present analysis because sufficient data were available only for olanzapine, risperidone and the no-medication group. Both female and male patients showed considerable weight gain after switch or initiate of olanzapine or risperidone, but meta-regression analyses did not show significant sex differences.
CONCLUSION: The present meta-analysis revealed that sex differences in AP-related weight gain have been under investigated hampering the detection of sex-specific patterns. In chronic patients switching to olanzapine or risperidone receiving short-or middle-term treatment, AP were associated with weight gain in both sex subgroups and no significant differences were reported.

PMID: 29602172 [PubMed - indexed for MEDLINE]

Factors influencing adherence to tuberculosis treatment in Asmara, Eritrea: a qualitative study.

J Health Popul Nutr. 2018 01 05;37(1):1

Authors: Gebreweld FH, Kifle MM, Gebremicheal FE, Simel LL, Gezae MM, Ghebreyesus SS, Mengsteab YT, Wahd NG

Abstract
BACKGROUND: Non-adherence to tuberculosis (TB) treatment is an important barrier for TB prevention and control. Poor adherence may result in prolonged disease infectiousness, drug resistance, relapse and death. The aim of this study was to assess factors influencing adherence to tuberculosis treatment in selected health facilities in Asmara, Eritrea.
METHODS: A qualitative study which included in-depth interviews with 12 TB patients, three focus group discussions in selected health facilities in which one group comprised eight patients and key informant interviews with three health workers. Data analysis was done by translating and transcribing the verbatim of the interviews and focus group discussions. Transcribed data was then analysed using thematic framework procedure.
RESULTS: This study found that patients lacked knowledge about the cause, transmission and duration of treatment of TB. The most common reason mentioned for discontinuing treatment was the patient "felt cured". Almost half of the respondents did not know the standard treatment duration and the consequences they face if they halt treatment. Patients reported losing their job when their diagnosis was known, were too ill to continue working or unable to find daily work due to time-consuming treatment arrangements. With few exceptions, the majority of patients reported that the short distance to the clinic encouraged them to attend regular treatment follow-up. Most of the respondents were unable to get enough food, leading to stress and feelings of hopelessness. Lack of social support for most of the patients was a critical factor for adherence as were stigma, medication side effects and long treatment duration. Recognized as an enabler to treatment adherence, health workers had good communication and positive attitude towards their patients.
CONCLUSION: Lack of knowledge, loss of income, stigma and lack of social support, drug side effects and long treatment duration emerged as important barriers for treatment adherence. Short distances to health facilities, good communication and accepting attitude of health care providers emerged as enablers for treatment adherence. For better treatment adherence, comprehensive health education at treatment sites, patient's family members and the community at large and strengthening of social support structures need to be addressed.

PMID: 29304840 [PubMed - indexed for MEDLINE]

[Rheumatological emergency on the edge of intensive care medicine].

Z Rheumatol. 2019 Oct 11;:

Authors: Härle P

Abstract
In rheumatological practice situations repeatedly occur where critical problems which need to be quickly addressed in order to prevent permanent damage to the patient. The focus of this article is on rapidly progressive inflammatory diseases, severe side effects of many medications and complications of infections during immunosuppressive treatment.

PMID: 31605194 [PubMed - as supplied by publisher]

Exploring the drug-induced anemia signals in children using electronic medical records.

Expert Opin Drug Saf. 2019 Oct;18(10):993-999

Authors: Fan DF, Yu YC, Ding XS, Nie XL, Wei R, Feng XY, Peng XX, Gao MM, Jia LL, Wang XL

Abstract
Objectives: The objectives were to identify drugs related with anemia in children and evaluate the novelty of these correlations. Methods: The authors established a two-step method for detecting the relationship between drugs and anemia using electronic medical records (EMRs), which were obtained from 247,136 patients in Beijing Children's Hospital between 2007 and 2017. The authors extracted potential drugs by mining cases for hemoglobin abnormalities from the EMR and then performed a retrospective cohort study to correlate them with anemia by calculating the matched odds ratios and 95% confidence interval using unconditional logistic regression analysis. Results: In total, nine positive drug-anemia associations were identified. Among them, the correlations of drugs fluconazole (OR 3.95; 95%CI: 2.65-5.87) and cefathiamidine (OR 3.49; 95%CI: 2.94-4.15) with anemia were considered new signals in both children and adults. Three associations of drugs, vancomycin, cefoperazone-sulbactam and ibuprofen, with anemia were considered new signals in children. Conclusion: The authors detected nine signals of drug-induced anemia, including two new signals in children and adults and three new signals in children. This study could serve as a model for using EMR and automatic mining to monitor adverse drug reaction signals in the pediatric population.

PMID: 31315002 [PubMed - indexed for MEDLINE]

Can doctors identify older patients at risk of medication harm following hospital discharge? A multicentre prospective study in the UK.

Br J Clin Pharmacol. 2018 10;84(10):2344-2351

Authors: Parekh N, Stevenson JM, Schiff R, Graham Davies J, Bremner S, Van der Cammen T, Harchowal J, Rajkumar C, Ali K, PRIME study group

Abstract
AIMS: Medication-related harm (MRH) is common in older adults following hospital discharge. In resource-limited health systems, interventions to reduce this risk can be targeted at high-risk patients. This study aims to determine whether (1) doctors can predict which older patients will experience MRH requiring healthcare following hospital discharge, (2) clinical experience and confidence in prediction influence the accuracy of the prediction.
METHODS: This was a multicentre observational prospective study involving five teaching hospitals in England between September 2013 and November 2015. Doctors discharging patients (aged ≥65 years) from medical wards predicted the likelihood of their patient experiencing MRH requiring healthcare (hospital readmission or community healthcare) in the initial 8-week period post-discharge. Patients were followed up by senior pharmacists to determine MRH occurrence.
RESULTS: Data of 1066 patients (83%) with completed predictions and follow-up, out of 1280 recruited patients, were analysed. Patients had a median age of 82 years (65-103 years), and 58% were female. Most predictions (85%) were made by junior doctors with less than 5 years' clinical experience. There was no relationship between doctors' predictions and patient MRH (OR 1.10, 95% CI 0.82-1.46, P = 0.53), irrespective of years of clinical experience. Doctors' predictions were more likely to be accurate when they reported higher confidence in their prediction, especially in predicting MRH-associated hospital readmissions (OR 1.58, 95% CI 1.42-1.76, P < 0.001).
CONCLUSIONS: Clinical judgement of doctors is not a reliable tool to predict MRH in older adults post-discharge.

PMID: 29957885 [PubMed - indexed for MEDLINE]

Is lithium monitoring NICE? Lithium monitoring in a UK secondary care setting.

J Psychopharmacol. 2018 04;32(4):408-415

Authors: Nikolova VL, Pattanaseri K, Hidalgo-Mazzei D, Taylor D, Young AH

Abstract
BACKGROUND: Lithium is widely used for the treatment of bipolar disorder. Owing to its narrow therapeutic index and side-effect profile, regular monitoring of serum levels, renal and thyroid function has been recommended by all major guidelines on lithium use.
OBJECTIVES: We investigated whether lithium monitoring during maintenance phase treatment in clinical practice meets the latest recommendation by the National Institute for Health and Clinical excellence (i.e. lithium levels between 0.6 and 1.0 mmol/L and lithium level, thyroid and renal function tests every 6 months) in one of the largest mental health organizations in Europe, the South London and Maudsley (SLaM) NHS Foundation Trust.
METHODS: Retrospective data were extracted from SLaM's Clinical Record Interactive Search (CRIS) system. Adult patients with a psychiatric disorder who were on lithium at any point during the period January 2012-January 2016 and had at least one lithium level test result in the system were included in the analyses.
RESULTS: A total of 2639 lithium level tests results were retrieved for 412 patients. Overall, the serum level was within the recommended range in 50.7% of all tests, below the range in 42.4% and above in 6.9%. Lithium level, renal and thyroid function tests were performed at the recommended frequency of 6 months (or less) in 76.2%, 72.7% and 60.2% of patients, respectively.
CONCLUSION: These data demonstrate that there is a gap between the NICE 2014 recommendation and lithium monitoring practice in secondary care, with a high number of lithium level results below the therapeutic minimum. Reminder strategies for secondary care practitioners, shared care agreements or a central registry for lithium users could improve monitoring performance.

PMID: 29552933 [PubMed - indexed for MEDLINE]

Efficacy and safety of sacubitril/valsartan in patients with essential hypertension uncontrolled by olmesartan: A randomized, double-blind, 8-week study.

J Clin Hypertens (Greenwich). 2018 01;20(1):150-158

Authors: Cheung DG, Aizenberg D, Gorbunov V, Hafeez K, Chen CW, Zhang J

Abstract
A majority of patients with hypertension fail to achieve blood pressure (BP) control despite treatment with commonly prescribed drugs. This randomized, double-blind phase III trial assessed the superiority of sacubitril/valsartan 200 mg (97/103 mg) to continued olmesartan 20 mg in reducing ambulatory systolic BP after 8-week treatment in patients with mild to moderate essential hypertension uncontrolled with olmesartan 20 mg alone. A total of 376 patients were randomized to receive either sacubitril/valsartan (n = 188) or olmesartan (n = 188). Superior reductions in 24-hour mean ambulatory systolic BP were observed in the sacubitril/valsartan group vs the olmesartan group (-4.3 mm Hg vs -1.1 mm Hg, P < .001). Reductions in 24-hour mean ambulatory diastolic BP and pulse pressure and office systolic BP and diastolic BP were significantly greater with sacubitril/valsartan vs olmesartan (P < .014). A greater proportion of patients achieved BP control with sacubitril/valsartan vs olmesartan. The overall incidence of adverse events was comparable between the groups. Compared with continued olmesartan, sacubitril/valsartan was more effective and generally safe in patients with hypertension uncontrolled with olmesartan 20 mg.

PMID: 29338113 [PubMed - indexed for MEDLINE]

Use of Medicines that May Exacerbate Heart Failure in Older Adults: Therapeutic Complexity of Multimorbidity.

Drugs Aging. 2019 05;36(5):471-479

Authors: Caughey GE, Shakib S, Barratt JD, Roughead EE

Abstract
BACKGROUND: Multimorbidity is common in older patients with heart failure (HF), complicating therapeutic management and increasing the risk of harm.
OBJECTIVE: This study sought to examine the prevalence of medicines for the treatment of comorbid conditions potentially associated with harm in older people, before and after HF hospitalization.
METHODS: A retrospective cohort study of older people hospitalized with a primary diagnosis of HF over a 12-month period was conducted using administrative health claims data from the Department of Veterans' Affairs (DVA) Australia. We examined the prevalence of medicines that may exacerbate or worsen HF as defined by the American Heart Association (AHA) and Australian HF clinical guidelines, in the 30 days prior and 120 days before and after discharge for HF.
RESULTS: A total of 4069 older adults were hospitalized for HF during the study period; almost 60% (n = 2435) received at least one medicine associated with an increased risk of harm before hospitalization, with the majority (66.7%, n = 1623) dispensed in the 30 days prior. A small but significant reduction after hospitalization was observed, but 56% (n = 1638) received at least one of these medicines after hospitalization (p = 0.001). Over one-quarter received two or more medicines before hospitalization, and this only reduced to 22% post-hospitalization (p < 0.0001).
CONCLUSIONS: Little change in the prescribing of potentially harmful medicines for HF was observed; 56% of older adults received at least one following hospitalization for HF, highlighting the therapeutic complexity of multimorbidity in HF. Use of the AHA list to facilitate identification of potentially harmful medicines, followed by prioritization of treatment goals and appropriate risk mitigation are needed to facilitate reduction in hospitalization for patients with HF with multimorbidity.

PMID: 30875020 [PubMed - indexed for MEDLINE]

Potentially Inappropriate Prescribing and Related Hospital Admissions in Geriatric Patients: A Comparative Analysis between the STOPP and START Criteria Versions 1 and 2.

Drugs Aging. 2019 05;36(5):453-459

Authors: Thevelin S, Mounaouar LE, Marien S, Boland B, Henrard S, Dalleur O

Abstract
BACKGROUND: Older persons are at significant risk of drug-related admissions (DRAs). We previously demonstrated that 27% of hospitalizations in geriatric patients were associated with potentially inappropriate medicines (PIMs) and/or potential prescribing omissions (PPOs) identified by the Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) criteria version 1 (v1). The updated STOPP/START criteria version 2 (v2) comprised a 31% increase in prescribing criteria.
OBJECTIVE: As a secondary analysis of our study conducted in 2008, we aimed to compare the prevalence and types of DRAs identified by STOPP/START.v1 and STOPP/START.v2.
METHODS: We applied the STOPP/START.v2 criteria to a subset of 100 consecutively admitted geriatric patients selected from our original cross-sectional study of 302 patients. A geriatrician and a pharmacist adjudicated whether the identified PIMs and PPOs were related to acute hospitalization. Admissions were defined as DRAs if the identified PIM(s) and/or PPO(s) were related to the main cause of admission or played a significant contributory role in the admission.
RESULTS: The median patient age was 83 years and the median number of medications at home was 8. Compared with STOPP/START.v1, STOPP/START.v2 not only yielded more instances of inappropriate prescribing but also targeted significantly more PIMs and PPOs associated with preventable DRAs (23% vs. 40% of all admissions, p < 0.001). PIMs of fall-risk-increasing drugs, and PPOs of musculoskeletal and cardiovascular system drugs, were most frequently associated with DRAs.
CONCLUSION: The latter instances of inappropriate prescribing with major clinical relevance warrant particular attention during medication review in older persons.

PMID: 30694444 [PubMed - indexed for MEDLINE]

Addressing New Diagnostic and Treatment Challenges Associated With a New Age of Cancer Treatment.

Ann Emerg Med. 2019 01;73(1):88-90

Authors: Bischof JJ, Presley CJ, Caterino JM

PMID: 30243546 [PubMed - indexed for MEDLINE]

Low to Intermediate Dose Atropine Administration During Dobutamine Stress Echocardiography in the Pre-Liver Transplant Population.

Prog Transplant. 2018 12;28(4):361-367

Authors: Snipelisky D, Shipman J, Olson N, Pellikka P, Aqel B, McCully R, Watt K

Abstract
INTRODUCTION: Dobutamine stress echocardiography (DSE) is frequently used to screen for obstructive coronary artery disease in the pre-liver transplant evaluation. Although atropine is a commonly used adjunctive medication, no study has evaluated its side effect profile in patients with end-stage liver disease (ESLD).
RESEARCH QUESTION: What is the safety of atropine in candidates undergoing pre-liver transplant evaluation when atropine is used in stress testing?
DESIGN: This multicenter, prospective study enrolled patients over a 6-month period undergoing pre-liver transplant evaluation. Each patient completed a questionnaire assessing anticholinergic-related symptoms within 24 hours of testing and 48 hours following. Comparisons were made among patients receiving any atropine dose versus those who did not and among patients receiving at least 1 mg atropine and those receiving less/none.
RESULTS: Forty patients were evaluated, and 32 (80%) had adjunctive atropine administered. No differences in clinical characteristics were noted. In comparisons among patients receiving any dose of atropine with those who did not, questionnaire results indicated a higher rate of nausea prior to testing and higher overall symptom severity following testing in patients not receiving atropine. In comparisons among patients receiving less than 1 mg atropine with those receiving at least 1 mg atropine, no difference in pre- or posttesting questionnaire responses was present. No patient in the study required reversal agents or hospitalization within 7 days of testing.
CONCLUSIONS: Atropine, a hepatically metabolized medication, did not predispose patients with ESLD to an increased symptom burden, and clinical outcomes related to DSE were unaffected.

PMID: 30222085 [PubMed - indexed for MEDLINE]

A novel multi-parametric high content screening assay in ciPTEC-OAT1 to predict drug-induced nephrotoxicity during drug discovery.

Arch Toxicol. 2018 10;92(10):3175-3190

Authors: Sjögren AK, Breitholtz K, Ahlberg E, Milton L, Forsgard M, Persson M, Stahl SH, Wilmer MJ, Hornberg JJ

Abstract
Drug-induced nephrotoxicity is a major concern in the clinic and hampers the use of available treatments as well as the development of innovative medicines. It is typically discovered late during drug development, which reflects a lack of in vitro nephrotoxicity assays available that can be employed readily in early drug discovery, to identify and hence steer away from the risk. Here, we report the development of a high content screening assay in ciPTEC-OAT1, a proximal tubular cell line that expresses several relevant renal transporters, using five fluorescent dyes to quantify cell health parameters. We used a validation set of 62 drugs, tested across a relevant concentration range compared to their exposure in humans, to develop a model that integrates multi-parametric data and drug exposure information, which identified most proximal tubular toxic drugs tested (sensitivity 75%) without any false positives (specificity 100%). Due to the relatively high throughput (straight-forward assay protocol, 96-well format, cost-effective) the assay is compatible with the needs in the early drug discovery setting to enable identification, quantification and subsequent mitigation of the risk for nephrotoxicity.

PMID: 30155723 [PubMed - indexed for MEDLINE]

Risk of renal events during tenofovir disoproxil fumarate and entecavir antiviral prophylaxis in HBsAg-positive cancer patients undergoing chemotherapy.

J Viral Hepat. 2018 12;25(12):1599-1607

Authors: Lee IC, Chao Y, Li CP, Su CW, Lan KH, Lin HC, Hou MC, Huang YH

Abstract
The risk of renal events in HBsAg-positive cancer patients receiving tenofovir disoproxil fumarate (TDF) or entecavir (ETV) antiviral prophylaxis during chemotherapy has not been evaluated. This study aimed to evaluate the renal safety of TDF and ETV during chemotherapy. Consecutive, 219 HBsAg-positive cancer patients treated with TDF (n = 106) or ETV (n = 113) for antiviral prophylaxis during chemotherapy with baseline serum creatinine (SCr) <1.2 mg/dL were retrospectively enrolled. Serial SCr levels and estimated glomerular filtration rate (eGFR) were monitored. The incidence of acute kidney injury (AKI) during antiviral prophylaxis was 33% and 38.9% in TDF and ETV groups, respectively (P = 0.441), while the incidence of sustained kidney injury was 11.3% and 11.5%, respectively (P = 1.000). By multivariate analysis, diuretics use (hazard ratio (HR) = 2.011, P = 0.042) and serum albumin levels (HR = 0.441, P = 0.001) were independent predictors of AKI; serum albumin levels (HR = 0.252, P = 0.002) was the only factor associated with sustained kidney injury; age (HR = 2.752, P < 0.001), baseline SCr levels (HR = 3.386, P < 0.001), and serum albumin levels (HR = 0.437, P = 0.001) were factors associated with a new eGFR <60 mL/min. 34.9% of patients in TDF group and 35.4% in ETV group had deteriorated chronic kidney disease (CKD) stage at the end of follow-up, respectively. There were no significant differences in the risk of renal events or CKD stage migration between TDF and ETV groups. Renal events may develop in about one-third of HBsAg-positive cancer patients undergoing chemotherapy. The risk of renal function impairment was comparable between patients treated with TDF and ETV antiviral prophylaxis.

PMID: 30125436 [PubMed - indexed for MEDLINE]

Amantadine Extended-Release (GOCOVRI™): A Review in Levodopa-Induced Dyskinesia in Parkinson's Disease.

CNS Drugs. 2018 08;32(8):797-806

Authors: Paik J, Keam SJ

Abstract
Amantadine extended-release (ER) capsules (GOCOVRI™) are approved in the USA for the treatment of dyskinesia in patients with Parkinson's disease (PD) receiving levodopa-based therapy, with or without concomitant dopaminergic medications. With a recommended dosage of 274 mg once daily at bedtime, this new formulation of amantadine allows a more gradual time to peak plasma amantadine concentration and higher drug concentrations in the morning and throughout the day, the time period when levodopa-induced dyskinesia (LID) is the most problematic. In 13-week (EASE LID 3) and 25-week (EASE LID), randomized, double-blind phase III trials, once-daily amantadine ER 274 mg capsules significantly improved levodopa-induced dyskinesia (LID), while also increasing ON time without troublesome dyskinesia and reducing OFF time and ON time with troublesome dyskinesia from the morning and throughout the day, compared with placebo. In the ongoing, longer-term EASE LID 2 study (with interim results reported for up to 64 weeks), patients previously treated with amantadine ER maintained improvements in LID, as per patient-reported Unified Dyskinesia Rating Scale (UDysRS) scoring and ON/OFF times. Amantadine ER was generally well tolerated, with most adverse events (AEs) being transient and mild or moderate in severity. The most common (incidence > 15%) treatment-related AEs in the placebo-controlled trials were hallucinations, dizziness, dry mouth and peripheral oedema. While long-term data are needed to establish durability of response and safety, including the completion of the ≈ 2-year EASE LID 2 study, current evidence indicates that amantadine ER is an effective treatment option to consider in the management of LID in PD patients.

PMID: 30088203 [PubMed - indexed for MEDLINE]

Safety and Efficiency of Intravenous Push Lacosamide Administration.

Neurocrit Care. 2018 Dec;29(3):491-495

Authors: Davidson KE, Newell J, Alsherbini K, Krushinski J, Jones GM

Abstract
BACKGROUND/OBJECTIVE: Intravenous (IV) lacosamide use for status epilepticus has increased in recent years and is recommended for refractory status epilepticus by current guidelines. Per the lacosamide package labeling, the preferred route of administration is diluted and infused over 30-60 min; however, administration undiluted is also acceptable and recent literature demonstrated safety at a maximum rate of 80 mg per minute (Kellinghaus et al. in Acta Neurol Scand 123:137-141, 2011). Undiluted administration as an IV push has potential to increase efficiency of administration to patients needing urgent seizure control since it may be dispensed from automatic dispensing cabinets in patient care areas. This study aims to compare safety outcomes and efficiency of administration in patients receiving lacosamide IV push compared to IV piggyback.
METHODS: We present a single-center, retrospective cohort study of patients receiving lacosamide via IV piggyback or IV push from June 2016 to July 2017. Baseline characteristics, data related to potential safety concerns and timing of ordering, verification, and administration were collected. The primary safety outcomes were incidence of infusion site reactions, hypotension (systolic blood pressure [SBP] < 90 mm Hg), and bradycardia (heart rate [HR] < 50 beats per minute) documented within 2 h of each lacosamide dose. Secondary safety outcomes included the incidence of PR interval prolongation in patients with at least one electrocardiogram measured. The primary efficiency outcome was the time between order verification and administration.
RESULTS: Patients in the IV piggyback (n = 88) and IV push (n = 78) groups had similar baseline characteristics, initial dose, SBP, and HR. Hypotension (8 vs. 10.3%) and bradycardia (2.3 vs. 2.6%) rates were similar among both groups (p > 0.05). Only one patient in each group had documented PR prolongation, and no documented infusion reactions occurred. Median time from order verification to administration was significantly reduced in the IV push group (35 min vs. 1 h 49 min; p < 0.001).
CONCLUSIONS: Administration of lacosamide via IV push results in similar adverse effect rates to IV piggyback preparations with more efficient time to administration.

PMID: 29949010 [PubMed - indexed for MEDLINE]

Adverse Drug Reactions Reported by Healthcare Professionals: Reaction Characteristics and Time to Reporting.

J Clin Pharmacol. 2018 10;58(10):1332-1339

Authors: Aung AK, Tang MJ, Adler NR, de Menezes SL, Goh MSY, Tee HW, Trubiano JA, Puy R, Zubrinich CM, Graudins LV

Abstract
We describe adverse drug reaction (ADR) reporting characteristics and factors contributing to length of time to report by healthcare professionals. This is a retrospective study of voluntary reports to an Australian healthcare ADR Review Committee over a 2-year period (2015-2016). Descriptive and univariate models were used for outcomes, employing standardized ADR definitions. Hospital pharmacists reported 84.8% of the 555 ADRs: 70.3% were hospital onset reactions, and 71.7% were at least of moderate severity. Immunologically mediated reactions were most commonly reported (409, 73.7%). The median time to submit an ADR report was 3 (interquartile range 1-10) days. Longer median times to reporting were associated with multiple implicated agents and delayed hypersensitivity reactions, especially severe cutaneous adverse reactions. A total of 650 medications were implicated that involved multiple agents in 165/555 (29.7%) reports. Antimicrobials were the most commonly implicated agents. Immunologically mediated reactions were most commonly associated with antimicrobials and radiocontrast agents (P < .0001, odds ratio [OR] 3.6, 95%CI 2.4-5.5, and P = .04, OR 4.2, 95%CI 1.2-18.2, respectively). Opioids and psychoactive medications were more commonly implicated in nonimmunological reported ADRs (P = .0002, OR 3.9, 95%CI 1.9-7.9, and P < .0001, OR 11.4, 95%CI 4.6-27.8, respectively). Due to the predominant reporting of immunologically mediated reactions, a targeted education program is being planned to improve identification and accuracy of ADR reports, with the overall aim of improved management to ensure quality service provision and patient safety.

PMID: 29733431 [PubMed - indexed for MEDLINE]

Ex-Lax®.

Skinmed. 2018;16(1):49

Authors: Bernhardt M

PMID: 29551115 [PubMed - indexed for MEDLINE]