Use of Methenamine for Urinary Tract Infection Prophylaxis: Systematic Review of Recent Evidence.

INTRODUCTION AND HYPOTHESIS: Antibiotic resistance is an unavoidable consequence of antibiotic use and growing rates of resistance are an urgent issue. Methenamine is a non-antibiotic alternative used for urinary tract infection (UTI) prophylaxis. The objective of this review is to evaluate recently published literature regarding the efficacy and safety of methenamine for UTI prophylaxis. METHODS: PubMed, Embase, and CENTRAL databases were queried in March 2023 using the following search terms: urinary tract infection, cystitis, bacteriuria, or dysuria, and methenamine. Studies prior to 2012 were excluded from this review to focus on appraisal of the most recent evidence. Prospective and controlled retrospective trials were included for review. RESULTS: A total of seven studies (three prospective and four retrospective) met the inclusion criteria for review. Two of the 3 prospective studies demonstrated no or non-inferior differences in clinical efficacy to prevent recurrent UTIs between methenamine and antibiotic prophylaxis and the third showed decreased rates of UTI with methenamine use in patients with short-term indwelling catheters compared with cranberry alone. The retrospective studies consistently supported the efficacy and safety of methenamine for UTI prophylaxis in a variety of populations and clinical settings. Adverse effects reported with methenamine were similar to comparators and included nausea, abdominal pain, and headache. CONCLUSIONS: The use of methenamine for UTI prophylaxis was shown to be effective in a variety of settings without an increased risk of adverse effects compared with prophylactic antibiotics. Larger blinded clinical trials are needed to further define the role of methenamine in UTI prophylaxis.

Efficacy and safety of hydroxyzine for sleep in adults: Systematic review.

OBJECTIVE: The purpose of this systematic review is to assess the efficacy and safety of hydroxyzine for insomnia in adults. METHODS: A comprehensive literature search of PubMed, Embase, and CENTRAL databases was conducted to identify relevant published studies through October 2022 using the search terms: hydroxyzine and sleep, insomnia, sleep disorder or sleep initiation and maintenance disorders. Studies identified for review included prospective, interventional designs or cohort trials that reported impact of hydroxyzine on sleep in adults. Animal studies, case reports, non-English articles, letters to the editor, case studies, and conference abstracts were excluded. Data were extracted using a standardized systematic process. RESULTS: Five articles were identified for inclusion, including 1 open-label and 4 randomized controlled trials, evaluating a total of 207 patients receiving hydroxyzine 25 mg, 50 mg, or 100 mg at bedtime. Mixed efficacy was demonstrated in the sleep measures of sleep onset, sleep maintenance, and sleep quality. The most common adverse drug effect was dry mouth, although 4 of the 5 studies did not report safety outcomes. CONCLUSIONS: The studies in this review suggest hydroxyzine could be considered as a short-term treatment option for adults with insomnia for whom previous therapy was ineffective, not tolerated, or contraindicated. Additional long-term studies with an active comparator are needed to further establish its role in insomnia treatment.

Role of memantine in the prophylactic treatment of episodic migraine: A systematic review.

OBJECTIVE: The purpose of this systematic review is to assess the efficacy and safety of memantine for the prophylactic treatment of episodic migraine. BACKGROUND: Migraine is a prevalent chronic disease with significant costs to the health care system. Although various prophylactic treatment options are available, these medications have limitations based on efficacy, potential side effects, and patient preference. Memantine is an N-methyl-d-aspartate receptor antagonist used in dementia treatment that may have potential benefit for migraine prophylaxis. METHODS: A systematic search of PubMed, Embase, and CENTRAL databases was conducted to identify relevant published studies through December 2020 using the search terms: migraine disorders, migraine, headache disorders, or headache and memantine. Studies selected for the systematic review included prospective, interventional designs and evaluated memantine for prophylaxis of migraine. Animal studies, case reports, abstracts, review articles, protocols without results, and studies not written in English were excluded. Data were extracted using a standardized systematic process and included author, publication date, study design, sample size, patient characteristics, treatment regimen, clinical efficacy outcomes, and adverse drug effects. RESULTS: Four articles were identified for inclusion representing two prospective open-label studies and two randomized, double-blind trials, evaluating 183 patients on memantine overall. A reduction in number of migraine days and headache severity were shown in all four studies in the participants treated with memantine. The most common adverse effects included somnolence, sedation, and nausea, none of which were severe. CONCLUSION: The studies in this review establish that memantine has the potential for use as a treatment option for episodic migraine. Additional long-term studies using an active comparator would be useful to further elucidate its role.

Methylphenidate use in geriatric depression: A systematic review.

OBJECTIVES: Geriatric depression is common and is often associated with coexisting medical illnesses, cognitive dysfunction, or both. Treatment with pharmacotherapy is usually required, and many patients may not respond to initial therapy. Thus, there is a need for adjunctive treatment options. The objective of this systematic review is to assess the efficacy and safety of methylphenidate (MPH) in the treatment of geriatric depression. METHODS: PubMed (1946-December 2020) and Embase (1947-December 2020) were queried using the following search terms: geriatrics, aged, geriatric patient, or elderly and depressive disorder, depression, major depression or late-life depression, and MPH. Studies were included if they were a randomized-controlled trial or open-label trial that investigated use of MPH for treatment of depression in adults aged 60 years and older. RESULTS: After screening per the inclusion criteria, five prospective trials were included. All studies found improvement in depressive symptoms with use of MPH or MPH combined with citalopram. Study durations ranged from 8 to 16 weeks and MPH dosing ranged from 5 to 90 mg per day. CONCLUSIONS: Based on the reviewed literature, MPH appears to be most effective when combined with citalopram and used short-term. MPH should be initiated at a low dose and titrated up to 10 or 20 mg per day based on response. Larger, long-term trials are needed to further define the role of MPH in this population.

Cryotherapy for the prevention of chemotherapy-induced peripheral neuropathy: A systematic review.

OBJECTIVE: Chemotherapy induced peripheral neuropathy (CIPN) is an adverse effect of certain chemotherapy agents that can result in dose reductions, permanent nerve damage, and chronic pain. Although pharmacological agents have been studied in this setting, there is no standard of care for the prevention of CIPN. Thus, the objective of this systematic review is to assess the efficacy and safety of cryotherapy for the prevention of CIPN. DATA SOURCES: PubMed (1946 to February 2020) and Embase (1947 to February 2020) were utilized to conduct a literature search using the following search terms: antineoplastic agent(s), taxoid(s), or chemotherapy and neuralgia, peripheral nervous system diseases, peripheral neuropathy, or paclitaxel-induced peripheral neuropathy and cryotherapy, cryotherapy device, hypothermia, low temperature procedures, or ice. DATA SUMMARY: A total of 11 studies were included in the final assessment. Results of this systematic review indicate that the efficacy of cryotherapy in preventing CIPN is conflicting. This may be due to studies utilizing differing cryotherapy administration methods, study design, and including only a small number of patients. All included studies utilized cryotherapy with taxane-based chemotherapy treatments and cooling gloves and socks was the most common method of administration. Overall, cryotherapy was well-tolerated and no serious adverse effects were noted. CONCLUSIONS: Due to the absence of serious adverse effects, cryotherapy is a reasonable option to consider to prevent CIPN in patients receiving taxane-based chemotherapy. However, additional research is needed, including larger, better designed studies, to fully delineate the role of cryotherapy for CIPN.

Impact of prophylactic oseltamivir on INR in patients on stable warfarin therapy.

Influenza prophylaxis with oseltamivir is recommended for exposed high-risk patients. Patients with many comorbidities have an increased likelihood of co-administration of oseltamivir and warfarin. Evidence of a drug interaction is conflicting in the literature and is limited to a 5-day treatment course. This study evaluates the impact of prophylactic oseltamivir on international normalized ratio (INR) in patients taking warfarin. This retrospective cohort study conducted within the Veterans Health Administration included patients on warfarin who received oseltamivir for influenza prophylaxis. The primary endpoint was change in INR from baseline to day 10 of oseltamivir treatment. Secondary endpoints included change in INR based on renal function and duration of oseltamivir prophylaxis, trend in INR, and frequency of bleeding and thrombosis events. A total of 1041 patients were included and received oseltamivir for a mean of 12.9 days. The mean post-oseltamivir INR was significantly increased compared to the pre-oseltamivir INR (2.39 to 2.52; p < 0.001). Patients with a creatinine clearance of 31-60 mL/min had a significant increase in INR (2.40 to 2.59; p < 0.01). There was an increase in INR when oseltamivir was used for 7 or 8-10 days. Of included patients, 5.1% and 1.8% had a recorded thrombosis or bleeding event, respectively. There was a significant increase in INR in patients on chronic warfarin therapy and concomitant prophylactic oseltamivir, but this change may only be clinically significant for certain patient populations. The most impact on INR was within 7-10 days of oseltamivir initiation and in patients with impaired renal function.

Safety analysis of long-term phenazopyridine use for radiation cystitis.

BACKGROUND: Phenazopyridine is a urinary tract analgesic indicated for short-term treatment of irritation in the lower urinary tract. Despite the lack of evidence for extended use, it is often used in varying durations for supportive care for cancer patients with radiation-induced cystitis. The objective of this study was to compare the incidence of adverse drug reactions in patients with radiation cystitis receiving long-term phenazopyridine (>14-day supply) compared to a matched comparator group. METHODS: This retrospective cohort study compared adverse events among cancer patients with and without phenazopyridine exposure. Included patients received radiation and at least one chronic medication between 1 July 2008 and 30 June 2017. The phenazopyridine group also received >14-day supply of phenazopyridine during the study period. Patients were matched based on gender, age (±5 years), cancer diagnosis, and palliative or curative treatment intent. Data collection occurred at baseline, during the time of presumed exposure, and through the end of the study period for surveillance purposes. RESULTS: A total of 272 patients received phenazopyridine for >14-day supply during the study period. Of these, 90 patients were included and matched to an equal number of patients in the comparator group. The included patients were similar between groups and were largely male with a diagnosis of prostate cancer. Most patients received between a 30- and 60-day supply of phenazopyridine. There were a total of 13 adverse drug reactions in the phenazopyridine group and 18 in the comparator group (p = 0.32). No differences were identified between the phenazopyridine and comparator groups for the incidence of individual adverse drug reactions, emergency department visits, hospitalizations, or new diagnoses of hepatocellular or colorectal cancer. CONCLUSION: There was no difference in adverse drug reactions among patients receiving phenazopyridine for >14 days compared to a matched comparator group. The overall incidence of adverse events in both groups was low.

Treatment of Demodex-associated inflammatory skin conditions: A systematic review.

Bacterial folliculitis, rosacea, and other common skin conditions have been linked to infestation by Demodex mites (human demodicosis). Currently, there is little guidance for treatment of inflammatory conditions associated with demodicosis. Thus, the objective of this review is to evaluate the efficacy and safety of treatments utilized for Demodex infestation. PubMed (1946 to January 2019) and Embase (1947 to January 2019) were searched with the following term combinations: Demodex mites, Demodex folliculitis, demodicosis, Demodex folliculorum, or Demodex brevis and articles evaluating treatment of body surface colonization with Demodex mites were included. Common interventions used for Demodex infestation include metronidazole-based therapies, permethrin, benzoyl benzoate, crotamiton, lindane, and sulfur. Short courses of metronidazole taken orally have shown efficacy in reducing Demodex density. Additionally, topical administration of permethrin daily or twice daily was shown to be efficacious across multiple studies. Crotamiton and benzyl benzoate were also efficacious treatments. Several therapies were associated with mild-to-moderate skin irritation. Due to limited data, no standard of care can be identified at this time. Efficacious treatment options may include permethrin, crotamiton, benzyl benzoate, and oral metronidazole; however, long-term efficacy has not been established.

The Role of Atomoxetine for Parkinson Disease-Related Executive Dysfunction: A Systematic Review.

BACKGROUND: Atomoxetine selectively inhibits the reuptake of norepinephrine. Given the noradrenergic system's role in executive function, pharmacotherapy options that affect norepinephrine are of particular clinical interest in Parkinson disease-related executive dysfunction. OBJECTIVE: The aim of this study was to assess the efficacy and safety of atomoxetine for Parkinson disease-related executive dysfunction. METHODS: MEDLINE (1946 to May 2018) and EMBASE (1947 to May 2018) were queried using the search term combination: Parkinson's disease, Parkinson disease, inhibition, impulse behavior, impulse control disorder, executive function, executive dysfunction, cognition, cognitive dysfunction, cognitive defect, response inhibition, strategic planning, strategy, or verbal fluency and atomoxetine hydrochloride or atomoxetine. Studies analyzed for relevance evaluated clinical outcomes of patients treated with atomoxetine for Parkinson disease-related executive dysfunction. Studies appropriate to the objective were evaluated, including 1 open-label flexible dose trial, 2 placebo-controlled longitudinal trials, and 4 placebo-controlled crossover single-dose trials. RESULTS: In patients with Parkinson disease, treatment with atomoxetine resulted in improvements in several markers of executive dysfunction including impulsivity, risk taking, and global cognition. Study durations ranged from single-dose trials to 10 weeks and used varying doses of atomoxetine. Atomoxetine was well tolerated in most studies with some reports of gastrointestinal adverse effects and insomnia. CONCLUSIONS: Based on the reviewed literature, atomoxetine continues to be a therapy of interest for the treatment of executive dysfunction in patients with Parkinson disease. Larger long-term trials are necessary to further define the role of atomoxetine for patients with Parkinson disease-related executive dysfunction.

The role of mirtazapine in patients with fibromyalgia: a systematic review.

Mirtazapine is commonly used to treat major depressive disorder. Due to its effects on multiple neurotransmitters, it has been investigated for possible benefits in patients with fibromyalgia. The objective of this systematic review is to assess the efficacy and safety of mirtazapine in the treatment of patients with fibromyalgia. Pubmed (1946-May 2018), Embase (1947-May 2018), CENTRAL, and ClinicalTrials.gov were queried using the search term combination: fibromyalgia, pain, chronic pain, neuralgia, neuropathic pain, chronic widespread pain, or chronic pain syndrome and mirtazapine. Studies appropriate to the objective were evaluated, including three randomized, placebo-controlled trials and one open-label trial, investigating the effect of mirtazapine in patients with fibromyalgia. In patients with fibromyalgia, treatment with mirtazapine resulted in improvements in pain, sleep, and quality of life. Study durations ranged from 6 to 13 weeks and studies used varying dosing strategies for mirtazapine. Minor occurrences of somnolence, weight gain, nasopharyngitis, dry mouth, and increased appetite were reported with mirtazapine use. Based on the reviewed literature, mirtazapine appears to be a promising therapy to improve pain, sleep, and quality of life in patients with fibromyalgia. These benefits were demonstrated in patients that were treatment naïve and those that had failed previous therapies. Additional clinical evidence through larger and longer length trials would be of benefit to further define the role of mirtazapine for patients with fibromyalgia.

Ibrutinib-associated tumor lysis syndrome in chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma: A case series and review of the literature.

Background Tumor lysis syndrome results when intracellular contents are released during cell lysis. Ibrutinib, a Bruton tyrosine kinase inhibitor, is used for the treatment of chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenström's macroglobulinemia, mantle cell lymphoma, and marginal zone lymphoma. Tumor lysis syndrome caused by ibrutinib therapy is potentially life threatening, but is rare and not often reported in clinical trials. Objective The purpose of this case series is to describe the occurrence of tumor lysis syndrome in two patients initiated on ibrutinib, and to highlight the importance of close monitoring during therapy. Discussion One patient with chronic lymphocytic leukemia/small lymphocytic lymphoma and one patient with mantle cell lymphoma developed laboratory and clinical tumor lysis syndrome following initiation of ibrutinib therapy. Assessment with the Naranjo Adverse Drug Reaction Probability Scale indicated one probable relationship and one possible relationship between ibrutinib therapy and tumor lysis syndrome. There were additional factors that may have confounded the laboratory and clinical factors observed, including baseline laboratory values and concurrent medications. Both patients were managed with supportive therapies. A literature review identified five additional reported cases of tumor lysis syndrome following ibrutinib therapy. Conclusion This case series identifies one patient with a probable relationship and one patient with a possible relationship between the development of tumor lysis syndrome and treatment with ibrutinib. Although uncommon, proper attention should be given to monitoring for this adverse drug reaction and appropriate follow-up should occur despite ibrutinib's ease of administration.

Medication Safety in Clinical Trials: Role of the Pharmacist in Optimizing Practice, Collaboration, and Education to Reduce Errors.

Standardized safety practices for investigational drugs in clinical research protocols are limited and the vast majority of research pharmacists have concerns regarding its safety. Identified areas for medication safety risks include protocol complexity, medication ordering, and the processes for packaging, storage, and dispensing investigational medications. Inclusion of a pharmacist creates multiple mechanisms to promote safety and improve the quality of clinical research. This is accomplished through collaborating in the development of a research protocol, reviewing as a member of an advisory committee, developing mechanisms that contribute to safety, and assuring compliance with local and national regulations and standards. Ultimately, the profession of pharmacy has foundational responsibility for assuring the safe and effective use of medications, including investigational drugs in clinical research. It is through multidisciplinary collaboration that a research study will attain the highest standards for safety and maximize the quality and effectiveness of the data obtained in the clinical trial.

Application of the Layered Learning Practice Model in an Academic Medical Center.

The layered learning practice model (LLPM) is a teaching strategy designed to train residents to precept students and other residents with the oversight of a seasoned clinical pharmacist. This model serves as a tool for residency programs to implement quality precepting opportunities and learning experiences as they look for new ways to integrate multiple learners into the practice setting. The levels of the LLPM include a senior preceptor, resident, and student. It is best implemented through utilization of 4 steps: orientation to the LLPM, preexperience planning, implementation, and postexperience evaluation. Orientation introduces preceptors and residents to the LLPM and outlines expectations for each precepting level. Preexperience planning allows the resident to take a leadership role in developing calendars, rotation activities, rubrics, and activities that match goals and objectives. For implementation, the senior preceptor maintains an active role with all learners; the resident serves as the student's primary preceptor and is responsible for incorporating the student into clinical activities, evaluating student work, and providing feedback. Postexperience evaluation is designed to solicit and provide feedback to the resident and student and to identify recommendations for improvement of the LLPM. Overall, the LLPM is a multilayered model incorporating the expertise and unique learning positions of the senior preceptor, resident, and student. Redistributing components of the senior preceptor's responsibility amongst learners may result in expansion of patient care and clinical services and help satisfy the increasing demands placed on pharmacists.

Pregabalin for the Treatment of Restless Legs Syndrome.

OBJECTIVE: To evaluate the efficacy and safety of pregabalin for the treatment of restless legs syndrome (RLS). DATA SOURCES: A search of the MEDLINE database (1956-February 2016) and EMBASE (1957-February 2016) was conducted, using the terms pregabalin and restless legs syndrome In addition, a manual review of the references cited in each publication identified from the database search was conducted to identify relevant articles. STUDY SELECTION AND DATA EXTRACTION: All English-language, peer-reviewed publications were evaluated for relevance. From an initial review of 285 articles, 5 clinical trials were included in the final analysis. DATA SYNTHESIS: Pregabalin is an analog of γ-aminobutyric acid that exhibits antinociceptive and anticonvulsant activity by binding to voltage-gated calcium channels in the central nervous system. Studies of pregabalin have demonstrated efficacy through significant reductions in mean International RLS Scale scores and wake after sleep onset scores, and it had a lower rate of augmentation than pramipexole treatment. Study durations ranged from 6 to 52 weeks, with doses ranging from 150 to 600 mg daily. The most common adverse effects associated with pregabalin use in all studies included dizziness and somnolence. CONCLUSIONS: Clinical evidence suggests that pregabalin may improve symptoms of RLS and reduce disturbances in sleep, resulting in improvements in quality of life for patients affected by the disease. Pregabalin is considered to be relatively safe and poses a minimal risk of augmentation unlike current recommended first-line treatments for RLS. Thus, evidence suggests that pregabalin is a reasonable therapeutic option for the treatment of RLS.

Inhaler misuse in an older adult population.

OBJECTIVE: To determine the prevalence of inhaler misuse in an older adult population. DESIGN: Prospective observational study. SETTING: Two primary care outpatient clinics in a Veterans Affairs Medical Center in North Carolina. PARTICIPANTS: Male veterans 65 years of age and older (N = 24) prescribed a pressurized metered dose inhaler (pMDI) or a dry powder inhaler (DPI). MEASUREMENTS: Inhaler technique was evaluated using placebo inhaler devices and a standardized technique assessment form that included critical steps. Potential risk factors for misuse were obtained from the medical record, and the time for technique evaluation was collected. MAIN RESULTS: Study participants yielded 44 unique device observations. Patients were male with an average age of 82 years. All patients made at least one error, with a mean error rate of 2.5 errors/patient/inhaler, while 20 of 24 (83%) patients made at least one critical error with a mean error rate of 1.2 critical errors/patient/inhaler. Assessment of inhaler technique required 2.3 minutes/inhaler. Critical errors were made during 15 of 19 (79%) pMDI observations and 22 of 25 (88%) DPI observations. Patients with multiple inhalers or a history of stroke committed errors more often, although no risk factors demonstrated meaningful differences in error rates. CONCLUSIONS: Inhaler misuse in older adults is common, including committing critical errors that have been shown to reduce drug delivery. The time necessary for technique evaluation is relatively small. The high rate of misuse observed should serve as motivation for increased vigilance, individualized technique education, and routine re-assessment in the highly heterogeneous older adult population.

Methods to Promote Preceptor Scholarship through Resident Collaboration.

Preceptor participation in scholarly endeavors is recognized in the American Society of Health-System Pharmacists's (ASHP) residency accreditation standards as a method to demonstrate commitment and contribute to the profession of pharmacy. Although workplace demands and position responsibilities may not allow adequate time for preceptors to pursue scholarly activities, collaboration with pharmacy residents in a structured environment can be mutually beneficial and aid in the professional development of the resident and preceptor. The goal of this article is to provide preceptors with a description of activities suitable for collaboration with residents and with tips to ensure success within the residency year.

Galantamine-associated nightmares and anxiety.

BACKGROUND: This case report describes recurrent nightmares and anxiety possibly caused by the administration and rapid dose titration of galantamine. CASE SUMMARY: A 90-year-old male with Alzheimer's disease was initiated on galantamine 4 mg twice daily for 10 days, followed by 8 mg twice daily thereafter. On followup to the geriatric clinic, the patient reported complaints of nightmares and associated anxiety. The occurrences of nightmares developed after initiating galantamine and temporally increased with galantamine titration. After discontinuation of galantamine, the patient reported no further occurrences of nightmares or anxiety and memory function remained stable. CONCLUSION: Galantamine-associated nightmares are an uncommon adverse event and may have been exacerbated by rapid titration. Although such adverse events are unlikely to cause harm in the patient, such sleep abnormalities have the potential to decrease a patient's quality of life and may require the need for alternative therapy.

Development of a specialty medication clinical dashboard to improve tumor necrosis factor-α inhibitor safety and adherence monitoring.

PURPOSE: To describe the development of a pilot specialty medication clinical dashboard targeting tumor necrosis factor (TNF)-α inhibitor therapy. SUMMARY: This was a quality improvement project conducted between August 2019 and April 2020. The dashboard was designed with collaboration between clinical pharmacists and specialty providers in rheumatology, gastroenterology, and dermatology. Data was queried from the Veterans Affairs Corporate Data Warehouse. Patients with an active prescription or intravenous order for a TNF-α inhibitor were included. Dashboard flag criteria focused on TNF-α inhibitor safety and adherence monitoring. Flag results from the dashboard were characterized from data captured at a single time point. For 431 patients on TNF-α inhibitor treatment at the institution, 304 flags corresponding to 223 unique patients (51.7%) were identified on the dashboard: 3% of patients had a new infection, 9% had overdue monitoring laboratory tests, 5% had a critical laboratory result, 2% were on 2 biologic agents, 27% were overdue for a refill, 6% had an emergency department visit, and 2% had an inpatient admission. No patients were flagged for heart failure exacerbation or new malignancy. Seventeen percent of patients were prescribed high-dose etanercept or adalimumab, representing a potential annual cost savings of $302,497 if 50% of these patients had their dose successfully reduced to labeled dosing. Opportunities for pharmacist intervention utilizing the dashboard were identified and characterized through chart review of flagged patients. CONCLUSION: Pharmacists have the opportunity to improve safety and adherence for TNF-α inhibitor therapy through use of a specialty medication clinical dashboard. The dashboard should be used in conjunction with collaborative practice protocols.