scholarly journals A review of a recently published guidelines' “strong recommendation” for therapeutic drug monitoring of olanzapine, haloperidol, perphenazine, and fluphenazine

2019 ◽  
Vol 9 (4) ◽  
pp. 287-293
Author(s):  
Christopher Noel
Keyword(s):  
United States ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Meta Analysis ◽  
Maintenance Phase ◽  
The United States ◽  
Therapeutic Drug ◽  
Reference Ranges ◽  
Strong Recommendation ◽  
Growing Body

Abstract Introduction In addition to clozapine, there is a growing body of evidence that supports therapeutic drug monitoring (TDM) for additional antipsychotics commonly used in the United States. Methods The Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) published TDM guidelines for several psychiatric medications. Sources were identified that the authors used to establish therapeutic reference ranges for haloperidol, fluphenazine, perphenazine, and olanzapine—4 antipsychotics commonly used in the United States with a “strong recommendation” for TDM. The sources were then reviewed for content and appropriateness for utilization in establishing the reference ranges. Results Olanzapine had 15 citations, haloperidol had 9, perphenazine had 4, and fluphenazine had 2. The studies' methods were reviewed along with the proposed therapeutic reference ranges. Discussion Several limitations of the guidelines were identified. Reference ranges were suggested based on studies of patients with various diagnoses; some patients had an acute exacerbation, and others were in a maintenance phase. An additional publication was identified that reviewed similar (and additional) TDM studies; those conclusions were in slight contrast with those of the AGNP guidelines. In the future, guidance should be given to those looking to conduct TDM studies to standardize methods and make meta-analysis of this data more feasible.

scholarly journals Thiopurines’ Metabolites and Drug Toxicity: A Meta-Analysis

2020 ◽  
Vol 9 (7) ◽  
pp. 2216
Author(s):  
Paula Sousa ◽  
Maria Manuela Estevinho ◽  
Cláudia Camila Dias ◽  
Paula Ministro ◽  
Uri Kopylov ◽  
...  
Keyword(s):  
Systematic Review ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Alanine Aminotransferase ◽  
Odds Ratio ◽  
Drug Toxicity ◽  
Meta Analysis ◽  
Therapeutic Drug ◽  
Gastrointestinal Intolerance ◽  
The Relationship

Many questions remain unanswered regarding therapeutic drug monitoring (TDM) utility with thiopurines. This study aims to establish a relationship between thiopurines’ metabolites and drug toxicity. We performed a systematic review with inclusion of studies evaluating the relationship between thiopurines’ metabolites and drug toxicity. Meta-analysis of mean difference (MD), correlations and odds ratio (OR) was performed. We identified 21,240 records, 72 of which were eligible for meta-analysis. Levels of 6-thioguanine nucleotides (6-TGN) were higher in patients with leukopenia (MD 127.06 pmol/8 × 108 RBC) and gastrointestinal intolerance (MD 201.46 pmol/8 × 108 RBC), and lower in patients with hepatotoxicity (MD −40.6 pmol × 108 RBC). We established a significant correlation between 6-TGN and leukocytes (r = −0.21), neutrophils (r = −0.24) and alanine aminotransferase levels (r = −0.24). OR for leukopenia in patients with elevated 6-TGN was 4.63 (95% CI 2.24; 9.57). An optimal cut-off of 135 pmol/8 × 108 RBC for leukopenia was calculated (sensitivity 75.4%; specificity 46.4%). 6-methylmercaptopurine ribonucleotides (6-MMPR) were significantly associated with hepatotoxicity (MD 3241.2 pmol/8 × 108 RBC; OR 4.28; 95% CI 3.20; 5.71). Levels of 6-MMPR measured in the first 8 weeks of treatment were associated with leukopenia. We conclude that TDM could be used to prevent thiopurines’ toxicity. As optimal metabolites level may vary according to indication, physicians may adapt posology to decrease toxicity without compromising efficacy.

Pharmacokinetic Properties of New Antiepileptic Drugs

2005 ◽  
Vol 18 (6) ◽  
pp. 444-460 ◽  
Author(s):  
Michele Y. Splinter
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Interactions ◽  
Antiepileptic Drugs ◽  
Drug Monitoring ◽  
The United States ◽  
Therapeutic Drug ◽  
Kinetic Properties ◽  
New Antiepileptic Drugs ◽  
Drug Concentrations ◽  
Pharmacokinetic Properties

Eight new antiepileptic drugs (AEDs) have been approved for use within the United States within the past decade. They are felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, and zonisamide. These afford clinicians with more options to increase efficacy and tolerability in the treatment of patients with epilepsy. Pharmacokinetic properties and drug interactions with other AEDs and other medications taken for comorbidities are individually discussed for each of these new agents. Drug concentrations are not routinely monitored for these newer agents, and there have been few studies designed to investigate their concentration-effect relationships. For most of these medications, the concentrations observed in responders and nonresponders overlap considerably and levels associated with efficacy are often associated with adverse events, complicating the definition of target ranges. Also, epilepsy manifests itself sporadically causing difficulty in clinically monitoring efficacy of medications. Therapeutic drug monitoring provides for the individualization of treatment for these agents, which is important because they demonstrate significant variability in inter- and intraindividual pharmaco-kinetic properties. Therapeutic drug monitoring also allows for identification of noncompliance, drug interactions, and toxicity. Current knowledge of the relationships between efficacy, toxicity, and drug concentrations is discussed.

Therapeutic drug monitoring (TDM) during maintenance phase treatment at a community mental health centre

2019 ◽  
Vol 27 (6) ◽  
pp. 637-640
Author(s):  
Tom Meehan ◽  
Hong Wang ◽  
Allan Drummond ◽  
Hazlin Lockman
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Inpatient Care ◽  
Health Centre ◽  
Maintenance Phase ◽  
Case Managers ◽  
Therapeutic Drug ◽  
Community Mental Health Centre ◽  
Mental Health Centre ◽  
Allocation Of Time

Objective: To assess the extent to which therapeutic drug monitoring during maintenance phase treatment with lithium and clozapine was performed according to an agreed protocol and to identify strategies that may support monitoring. Methods: Data concerning the prescribing and monitoring patterns of lithium for 31 patients and clozapine for 53 patients were collected retrospectively over a period of 2 years. Results: Adherence to clozapine monitoring throughout the study period was 90.5%, while the monitoring of lithium was less likely at 58.1% ( P < 0.001). While those prescribed lithium were less likely to adhere to prescribed dosing than those prescribed clozapine ( P < 0.007), they were also more likely to have a change of medication ( P < 0.005) and require admission to inpatient care ( P < 0.002). Conclusions: Despite the initiatives established to improve adherence to monitoring, there was a significantly lower level of lithium monitoring compared to that of clozapine. Strategies that are likely to support monitoring include the use of labels to clarify tests required, the use of a database to keep track of those requiring pathology tests and allocation of time each week for a nurse to work with medical staff and case managers to support monitoring.

Is Therapeutic Drug Monitoring for Anti-tumour Necrosis Factor Agents in Adults With Inflammatory Bowel Disease Ready for Standard of Care? A Systematic Review and Meta-analysis

2020 ◽  
Vol 14 (8) ◽  
pp. 1057-1065 ◽  
Author(s):  
Raj Shah ◽  
Gila R Hoffman ◽  
Mohammed El-Dallal ◽  
Alexander M Goldowsky ◽  
Ye Chen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Meta Analysis ◽  
Therapeutic Drug ◽  
Quality Of Evidence ◽  
Inflammatory Bowel

Abstract Introduction Using therapeutic drug monitoring [TDM] in adult patients with inflammatory bowel disease [IBD] remains controversial. We conducted a systematic review and meta-analysis to answer four clinical PICO [Population, Intervention, Comparator, Outcome] questions. Methods We searched MEDLINE, Embase, Web of Science, and Cochrane Central from inception to June 30, 2019. Remission was defined by the manuscripts’ definitions of clinical remission. Data were analysed using RevMan 5.3. Quality of evidence was assessed with GRADE methodology. Results We identified and screened 3365 abstracts and 11 articles. PICO 1 Reactive vs No TDM: six studies pooled showed 57.1% [257/450] failed to achieve remission following reactive TDM vs 44.7% [268/600] in the no TDM group (risk ratio [RR]: 1.14; 95% confidence interval [CI] 0.88–1.47). PICO 2 Proactive vs no TDM: five studies pooled showed 19.5% [75/384] failed to maintain remission in the proactive TDM group vs 33.4% [248/742] in the no TDM group [RR: 0.60; 95% CI 0.35–1.04]. PICO 3 Proactive vs Reactive TDM: two retrospective studies pooled showed 14.2% [26/183] failure to maintain remission in the proactive TDM group and 64.7% [119/184] in the reactive TDM group [RR: 0.22; 95% CI 0.15–0.32]. PICO 4 TDM [proactive/reactive] vs No TDM: we pooled 10 studies showing 39.7% [332/837] failed to achieve remission in the TDM [proactive/reactive] cohort vs 40.3% [428/1063] in the no TDM cohort [RR: 0.94; 95% CI 0.77–1.14]. Overall, the quality of evidence in each PICO was very low when using GRADE. Conclusions This meta-analysis shows that data supporting use of TDM in adults are limited and of very low quality. Further well-designed randomized controlled trials are needed to determine the place of TDM in clinical practice.

scholarly journals Utility of voriconazole therapeutic drug monitoring: a meta-analysis

2016 ◽  
Vol 71 (7) ◽  
pp. 1786-1799 ◽  
Author(s):  
Me-Linh Luong ◽  
Mona Al-Dabbagh ◽  
Andreas H. Groll ◽  
Zdenek Racil ◽  
Yasuhito Nannya ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Meta Analysis ◽  
Therapeutic Drug
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