Clozapine clinical toolkit optimizes inpatient clozapine monitoring.

Introduction: Clozapine is the most effective antipsychotic in the management of treatment-resistant schizophrenia; however, its use is challenging due to the risk of severe adverse effects. Despite the risks associated with clozapine, there is no mandatory monitoring in Canada beyond hematologic testing for agranulocytosis surveillance. This study focuses on the development, implementation, and evaluation of a clozapine clinical toolkit (CTK) targeted at optimizing inpatient clozapine use. Methods: A comprehensive literature review was conducted to identify clozapine best practices, experts were consulted, and a comprehensive clozapine CTK was developed and implemented at a large Canadian tertiary hospital in December 2018. To evaluate the CTK, a retrospective chart review was conducted to assess for change in guideline-concordant monitoring pre- and post- CTK implementation. Patients were included if they were > 18 years of age and received clozapine during inpatient admission. Results were analyzed using descriptive and inferential statistics. Results: Among the charts reviewed, 185 and 113 admissions met the pre- and post-CTK inclusion criteria, respectively. Staff used the CTK in the care of 96% of clozapine patients post implementation, and its use resulted in improvements in guideline-concordant monitoring for agranulocytosis and myocarditis. Discussion: Implementation of the clozapine CTK increased the concordance of clozapine monitoring with best practice recommendations. Future research is necessary to assess the impact of the CTK on clinical outcomes and patient satisfaction.

Outpatient Rapid Titration of Slow Release Oral Morphine for the Treatment of Opioid Use Disorder in a Canadian Setting: A Case Series.

INTRODUCTION: In the midst of unprecedented opioid overdose deaths, opioid agonist therapy induction strategies that allow for rapid titration to therapeutic doses for individuals at high risk of overdose are needed. Slow release oral morphine (SROM) is an effective treatment for opioid use disorder; however, current guideline-recommended titration strategies require weeks to achieve therapeutic dose for individuals with high opioid tolerance. Individuals may be lost to care or experience overdose due to ongoing use of unregulated opioids during this time. After years of experience titrating SROM doses rapidly in the inpatient setting, we developed a protocol using short-acting morphine (MOS) to allow for rapid SROM titration in the outpatient setting. CASES: Patients (n = 4) were eligible if they met the criteria for opioid use disorder and had evidence of high opioid tolerance. Patients received supervised MOS doses in the outpatient setting, which were consolidated into a 12-hour extended-release morphine dose (to a maximum of 500 mg) on the evening of the titration. The total titration-day MOS and 12-hour extended-release morphine were summed into the post-titration-day SROM dose, to a maximum of 1000 mg. DISCUSSION: In the cases described, substantial reductions in unregulated fentanyl use and social gains, such as obtaining housing, employment, and enrollment in inpatient treatment programs, were observed after rapid SROM titration. No overdoses occurred during rapid SROM titration or during SROM treatment. More research is needed to determine the role for rapid SROM titrations as a stabilization option for outpatients.

Characterization of Psychotropic PRN Medications in a Canadian Psychiatric Intensive Care Unit.

BACKGROUND: Pro re nata (PRN) antipsychotics and benzodiazepines are routinely used for the rapid stabilization of acutely agitated patients. Despite the popular use of PRN medications in mental health units, primary literature supporting efficacy and safety is poor, and there is no single universally accepted practice guideline. PRN psychotropic medications have the potential to cause adverse effects when used inappropriately. AIMS: Our objective was to characterize the prescribing, administration, and documentation practices of PRN psychotropic medications in a psychiatric intensive care unit. METHODS: We conducted a retrospective chart review of patients admitted to a 12-bed psychiatric intensive care unit between June and September 2018. All PRN antipsychotic and benzodiazepine orders, administrations, documentation practices, and attempted nonpharmacological strategies were assessed for each order and patient. Descriptive statistics were used to analyze data. RESULTS: Thirty-two patients with a total of 123 physicians' orders and 1,179 PRN administrations of antipsychotics and benzodiazepines were reviewed. Of the total administrations, 720 (61%) were combinations with at least two psychotropic agents. Forty-one (33%) physicians' orders had a prescribed indication, and 559 (47%) administrations had an attempted nonpharmacological method prior to PRN administration. Eight patients (25%) had antipsychotic PRN orders, which exceeded the total daily maximum dose. Three adverse drug effects were attributed to PRN administration. CONCLUSIONS: Areas of improvement that we identified included documentation practices of effectiveness of administered PRNs, prescriptions to include clear indications and dosage within the 24-hour maximum limits, and documentation of nonpharmacological methods utilized.

Clinical Pharmacokinetic Monitoring of Leflunomide in Renal Transplant Recipients with BK Virus Reactivation: A Review of the Literature.

Leflunomide is an immunosuppressive drug with in vitro and initial observational evidence of antiviral activity against BK virus (BKV), a pathogen that causes opportunistic infection upon reactivation in renal transplant recipients. Leflunomide is considered an ancillary option to immunosuppression reduction in the management of BKV reactivation. Plasma or blood concentrations of teriflunomide, the active metabolite of leflunomide, are commonly monitored because of high leflunomide doses being used, known inter-individual variability in pharmacokinetics, and hepatotoxicity risk. However, the utility of clinical pharmacokinetic monitoring for leflunomide is as yet unclear. A literature search of MEDLINE (1946-December 2016), EMBASE (1974-December 2016), the CENTRAL database, and Google Scholar was performed to identify relevant English-language articles. Further articles were identified from references in relevant literature. A previously published 9-step decision-making algorithm was used to assess the available literature and determine the utility of clinical pharmacokinetic monitoring for leflunomide. Teriflunomide is readily measurable in the plasma or blood, but a clear relationship between concentration and efficacy or toxicity is lacking, and its therapeutic range is not well-established. Efficacy and toxicity endpoints such as renal function and BKV clearance can be readily assessed without measuring teriflunomide concentrations. Pharmacokinetic parameters are affected by genetic polymorphisms in cytochrome P450 CYP2C19 and ABCG2 genes. Therefore, routine clinical pharmacokinetic monitoring of leflunomide cannot be recommended based on current available evidence. However, it may provide clinical benefit in difficult situations when patients demonstrate a lack of therapeutic response or exhibit signs of drug toxicity.