Therapeutic Drug Monitoring of Pazopanib in Renal Cell Carcinoma and Soft Tissue Sarcoma: A Systematic Review.

BACKGROUND: Pazopanib, an anti-angiogenic multitarget tyrosine kinase inhibitor, has been approved for the treatment of metastatic renal cell carcinoma and soft tissue sarcoma. However, its recommended dose does not always produce consistent outcomes, with some patients experiencing adverse effects or toxicity. This variability is due to differences in the systemic exposure to pazopanib. This review aimed to establish whether sufficient evidence exists for the routine or selective therapeutic drug monitoring of pazopanib in adult patients with approved indications. METHODS: A systematic search of the PubMed and Web of Science databases using search terms related to pazopanib and therapeutic drug monitoring yielded 186 and 275 articles, respectively. Ten articles associated with treatment outcomes or toxicity due to drug exposure were selected for review. RESULTS: The included studies were evaluated to determine the significance of the relationship between drug exposure/Ctrough and treatment outcomes and between drug exposure and toxicity. A relationship between exposure and treatment outcomes was observed in 5 studies, whereas the trend was nonsignificant in 4 studies. A relationship between exposure and toxicity was observed in 6 studies, whereas 2 studies did not find a significant relationship; significance was not reported in 3 studies. CONCLUSIONS: Sufficient evidence supports the therapeutic drug monitoring of pazopanib in adult patients to improve its efficacy and/or safety in the approved indications.

Effects of Plasmapheresis on Serum Lithium Levels in an ICU Patient with Bipolar Disorder: A Case Study.

ABSTRACT: This is a case description of a patient with bipolar disorder undergoing lithium therapy who received plasmapheresis for neuromyelitis optica spectrum disorder. Plasmapheresis resulted in lower and subtherapeutic serum lithium levels. Using therapeutic drug monitoring, a dose escalation of 80% was necessary to maintain therapeutic serum lithium levels. This underscores the importance of individualized therapy through therapeutic drug monitoring.

Enhanced fluorescent detection of oxaliplatin via BSA@copper nanoclusters: a targeted approach for cancer drug monitoring.

A new fluorescence sensing approach has been proposed for the precise determination of the anti-cancer drug oxaliplatin (Oxal-Pt). This method entails synthesizing blue-emitting copper nanoclusters (CuNCs) functionalized with bovine serum albumin (BSA) as the stabilizing agent. Upon excitation at 360 nm, the resultant probe exhibits emission at 460 nm. Notably, the fluorescence response of BSA@CuNCs substantially increases upon incubation with Oxal-Pt due to multiple binding interactions between the drug and the fluorescent probe. These interactions involve hydrogen bonding, hydrophobic interaction, and the high affinity between the SH groups (cysteine residues of BSA) and platinum (in Oxal-Pt). Consequently, this interaction induces aggregation-induced emission enhancement (AIEE) of BSA@CuNCs. The probe demonstrates a broad response range from 0.08 to 140.0 µM, along with a low detection limit of 20.0 nM, determined based on a signal-to-noise ratio of 3. Furthermore, the probe effectively detects Oxal-Pt in injections, human serum, and urine samples, yielding acceptable results. This study represents a significant advancement in the development of a straightforward and efficient sensor for monitoring platinum-containing anti-cancer drugs during chemotherapy.

Identification and characterization of critical values in therapeutic drug monitoring: a retrospective analysis.

Therapeutic drug monitoring (TDM) is a crucial clinical practice that improves pharmacological effectiveness and prevent severe drug-related adverse events. Timely reporting and intervention of critical values during TDM are essential for patient safety. In this study, we retrospectively analyzed the laboratory data to provide an overview of the incidence, distribution pattern and biochemical correlates of critical values during TDM. A total of 19,110 samples were tested for nine drug concentrations between January 1, 2019, and December 31, 2020. Of these, 241 critical values were identified in 165 patients. The most common critical values were vancomycin trough (63.4%), followed by tacrolimus trough (16.9%) and digoxin (15.2%). The primary sources of drug critical values were the department of general intensive care unit (ICU), cardiology, and surgery ICU. At baseline or the time of critical value, significant differences were found between the vancomycin, digoxin, and tacrolimus groups in terms of blood urea nitrogen (BUN), creatinine, N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and lymphocyte percentage, P < 0.05. Therefore, it is important to prioritize and closely monitor drug concentrations to reduce laboratory critical values during TDM.

Effect of Carbamazepine on Darunavir Trough Concentrations: When the Dose Can Make the Difference-A Case Study.

BACKGROUND: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations. METHODS: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia. RESULTS: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses. CONCLUSIONS: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.

Utility of TTR-INR guided warfarin adjustment protocol to improve time in therapeutic range in patients with atrial fibrillation receiving warfarin.

Warfarin remains the most prescribed oral anticoagulant of choice in atrial fibrillation (AF) patient in resource-limited settings. Despite evidence linking Time in Therapeutic Range (TTR) to patient outcomes, its use in clinical practice is not widespread. This prospective study explores the impact of a TTR-INR guided Warfarin adjustment protocol on TTR in AF patients. Conducted at the Warfarin clinic of King Chulalongkorn Memorial Hospital. TTR was calculated using the Rosendaal linear interpolation method at baseline, and then at 6 and 12 months post-protocol implementation. The primary outcome was the improvement in TTR following the protocol's implementation. The study analyzed 57 patients, with a mean age of 72 years and an even gender distribution. At baseline, 53% of patients had a TTR of less than 65%. However, TTR significantly improved from 65% at baseline to 80% after 12 months of protocol implementation (p < 0.001). Furthermore, there was a significant increase in the proportion of patients with a TTR of 65% or more, from 47 to 88% (p < 0.001). During the follow-up period in the first 12 months, three patients died, but no ischemic or major bleeding events occurred. The significant improvement in TTR after 12 months of protocol implementation suggests that this strategy could provide additional value in improving TTR and outcomes in AF patients receiving Warfarin.

Innovative LC-MS/MS method for therapeutic drug monitoring of fenfluramine and cannabidiol in the plasma of pediatric patients with epilepsy.

We present a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying fenfluramine (FFA), its active metabolite norfenfluramine (norFFA), and Epidyolex®, a pure cannabidiol (CBD) oral solution in plasma. Recently approved by the EMA for the adjunctive treatment of refractory seizures in patients with Dravet and Lennox-Gastaut syndromes aged above 2 years, FFA and CBD still do not have established therapeutic blood ranges, and thus need careful drug monitoring to manage potential pharmacokinetic and pharmacodynamic interactions. Our method, validated by ICH guidelines M10, utilizes a rapid extraction protocol from 100 µL of human plasma and a reversed-phase C-18 HPLC column, with deuterated internal standards. The Thermofisher Quantiva triple-quadrupole MS coupled with an Ultimate 3000 UHPLC allowed multiple reaction monitoring detection, ensuring precise analyte quantification. The assay exhibited linear responses across a broad spectrum of concentrations: ranging from 1.64 to 1000 ng/mL for both FFA and CBD, and from 0.82 to 500 ng/mL for norFFA. The method proves accurate and reproducible, free from matrix effect. Additionally, FFA stability in plasma at 4 °C and -20 °C for up to 7 days bolsters its clinical applicability. Plasma concentrations detected in patients samples, expressed as mean ± standard deviation, were 0.36 ± 0.09 ng/mL for FFA, 19.67 ± 1.22 ng/mL for norFFA. This method stands as a robust tool for therapeutic drug monitoring (TDM) of FFA and CBD, offering significant utility in assessing drug-drug interactions in co-treated patients, thus contributing to optimized patient care in complex therapeutic scenarios.

Utility of hydroxychloroquine laboratory monitoring in dermatologic and rheumatologic patients.

Hydroxychloroquine (HCQ) is an immunomodulator used in dermatology and rheumatology. Side effects may be observed on routine monitoring studies before they become clinically apparent. The goal of this retrospective chart review was to assess laboratory abnormalities in dermatologic and rheumatologic patients taking HCQ. Medical records of patients prescribed HCQ were retrospectively reviewed. Demographics, reported side effects, and parameters on baseline and follow-up complete blood count (CBC) and comprehensive metabolic panel (CMP) were recorded and graded. Laboratory abnormalities were considered severe if they were grade 3 or greater according to Common Terminology Criteria for Adverse Events v3.0 and persistent if they continued beyond subsequent laboratory testing. Of 646 eligible charts, 289 had monitoring studies for review. There were 35 severe (grade 3 or 4, 35/289; 12%) adverse events that developed, as noted on CBC or CMP. Of these 35 severe adverse events, 25 self-corrected on subsequent testing, and 10 (10/289, 3%) across 9 patients were persistent, including glomerular filtration rate, alanine transferase, alkaline phosphatase, glucose, hemoglobin and lymphopenia abnormalities. Of these 10 abnormalities, 7/10 (70%) were unlikely due to hydroxychloroquine use according to the calculated Naranjo score for each patient. Severe laboratory abnormalities while taking hydroxychloroquine are rare, even in a population with a high rate of comorbidities. Among the abnormalities observed, the majority of them (70%) were likely due to disease progression or a medication other than hydroxychloroquine. CBC and CMP monitoring for the reason of observing abnormalities while on HCQ should be at the discretion of the prescribing physician.

Needle-in-needle electrochemical sensor for in-vivo monitoring of anticancer drug etoposide.

Therapeutic drug monitoring (TDM) serves as a potent tool for adjusting drug concentration within a reasonable range. However, continuous monitoring of anticancer drugs in-vivo presents a significant challenge. Herein, we propose a needle-in-needle electrochemical sensor based on an acupuncture needle electrode, capable of monitoring the anticancer drug etoposide in the peritoneal cavity of living rats. The acupuncture needle was modified with Au nanoparticles and etoposide-templated molecularly imprinted polymer (MIP), resulting in high sensitivity and selectivity in the electrochemical detection of etoposide. The modified acupuncture needle (0.16 mm diameter) was anchored inside a syringe needle (1.40 mm diameter), allowing the outer syringe needle to protect the modified materials of the inner acupuncture needle during skin piercing. Due to the unique needle-in-needle design, high stability was obtained during in-vivo etoposide monitoring. Connecting to a smartphone-controlled portable electrochemical workstation, the needle-in-needle sensor offers great convenience in point-of-care TDM. Moreover, the electrode materials on the acupuncture needle were carefully characterized and optimized. Under the optimized conditions, low detection limits and wide linear range were achieved. This work provides new insights into acupuncture needle electrochemical sensors and further expands the feasibility for real-time and in-vivo detection.

Preoperative Drug Monitoring in Management of Patients with Hip Fracture on Treatment with Direct Oral Anticoagulants.

Purpose: Aim of the present study was to evaluate whether monitoring direct oral anticoagulant (DOAC) levels may improve management of anticoagulated patients who need surgery for hip fracture. Patients and Methods: A total of 147 out of 2231 (7.7%) patients with hip fracture admitted to a tertiary teaching hospital were on DOACs (group A), whereas 206 patients matched for age, sex, and type of fracture not on anticoagulant or P2Y12 platelet inhibitors were considered as control group (group B). Patients on DOACs were divided into two subgroups: A1 in which intervention was scheduled in relation to the last drug intake according to current guidelines, and A2 included patients in whom time of surgery (TTS) was defined according to DOAC levels. Neuraxial anesthesia was considered with DOAC levels <30 ng/mL, general anesthesia for levels in the range 30-50 ng/mL. Results and conclusions: TTS was significantly lower in controls than in DOAC patients: surgery within 48 hours was performed in 80.6% of group B versus 51% in group A (p<0.0001). In A2, 41 patients underwent surgery within 48 hours (56%) in comparison to 32 A1 patients (45.1%; p=0.03). TTS and length of hospitalization were on average 1 day lower in patients with assay of DOAC levels. Finally, 35/39 (89%) patients with DOAC levels <50 ng/mL had surgery within 48 hours (26 under neuraxial anesthesia, without any neurological complication, and 13 in general anesthesia). Conclusion: DOAC assay in patients with hip fracture may be useful for correct definition of time to surgery, particularly in patients who are candidates for neuraxial anesthesia. Two-thirds of patients with DOAC levels <50 ng/mL at 48 hours from last drug intake underwent uneventful neuraxial anesthesia, saving at least 24 hours in comparison to guidelines.

Evidence for Therapeutic Drug Monitoring of Atypical Antipsychotics.

Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic drugs used to treat schizophrenia, bipolar disorder, and related psychiatric conditions. The plasma concentration of antipsychotic drugs is a valid measure of the drug at its primary target structure in the brain, and therefore determines the efficacy and safety of these drugs. However, despite the well-known high variability in pharmacokinetics of these substances, psychiatric medication is usually administered in uniform dosage schedules. Therapeutic drug monitoring (TDM), as the specific method that can help personalised medicine in dose adjustment according to the characteristics of the individual patient, minimizing the risk of toxicity, monitoring adherence, and increasing cost-effectiveness in the treatment, thus seems to be an elegant tool to solve this problem. Non-response to therapeutic doses, uncertain adherence to medication, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM of SGAs. This review aims to summarize an overview of the current knowledge and evidence of the possibilities to tailor the dosage of selected SGAs using TDM, including the necessary pharmacokinetic parameters for personalised pharmacotherapy.

Monitorización terapéutica de los fármacos biológicos en la enfermedad inflamatoria intestinal. Documento de Posicionamiento del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) / Therapeutic drug monitoring in inflammatory bowel diseases. Position statement of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis

El tratamiento de la enfermedad inflamatoria intestinal (EII) ha sufrido una gran transformación tras la introducción de los fármacos biológicos. Gracias a ellos, los objetivos del tratamiento han evolucionado desde la respuesta y remisión clínica a objetivos más ambiciosos, como la remisión endoscópica o radiológica. Sin embargo, aunque los biológicos son muy eficaces, un porcentaje importante de pacientes no obtendrá una respuesta inicial o la perderá a lo largo del tiempo. Sabemos que existe una relación directa entre las concentraciones valle del biológico y su eficacia terapéutica, que cuanto más exigente sea el objetivo terapéutico serán necesarios niveles superiores del fármaco y que es frecuente la exposición insuficiente al mismo. La monitorización terapéutica de medicamentos biológicos, así como los modelos farmacocinéticos, nos brindan la posibilidad de ofrecer un enfoque personalizado del abordaje en pacientes con EII. Durante los últimos años se ha acumulado información relevante respecto a su utilidad durante o después de la inducción, así como en el mantenimiento del tratamiento biológico, en estrategias reactivas o proactivas y antes de la retirada o desintensificación del esquema.El objetivo de este documento es establecer recomendaciones sobre la utilidad de la monitorización terapéutica de biológicos en pacientes con EII, en los diferentes escenarios de la práctica clínica e identificar las áreas donde su utilidad es evidente, prometedora o controvertida. (AU)

The treatment of inflammatory bowel disease has undergone a significant transformation following the introduction of biologic drugs. Thanks to these drugs, treatment goals have evolved from clinical response and remission to more ambitious objectives, such as endoscopic or radiologic remission. However, even though biologics are highly effective, a significant percentage of patients will not achieve an initial response or may lose it over time. We know that there is a direct relationship between the trough concentrations of the biologic and its therapeutic efficacy, with more demanding therapeutic goals requiring higher drug levels, and inadequate exposure being common.Therapeutic drug monitoring of biologic medications, along with pharmacokinetic models, provides us with the possibility of offering a personalized approach to treatment for patients with IBD. Over the past few years, relevant information has accumulated regarding its utility during or after induction, as well as in the maintenance of biologic treatment, in reactive or proactive strategies, and prior to withdrawal or treatment de-escalation.The aim of this document is to establish recommendations regarding the utility of therapeutic drug monitoring of biologics in patients with inflammatory bowel disease, in different clinical practice scenarios, and to identify areas where its utility is evident, promising, or controversial. (AU)

Therapeutic Drug Monitoring of Levetiracetam in Different Trimesters of Pregnant Women with Epilepsy in a Tertiary Care Center: A Prospective Study.

BACKGROUND: Levetiracetam is the most commonly used antiepileptic drug in pregnant women due to its low teratogenic risk profile, favorable pharmacokinetic characteristics, and safety profile. Serum levels of levetiracetam vary in epilepsy during pregnancy. Therefore, the aim of the study was to evaluate the serum levels of levetiracetam during different trimesters of pregnancy by using therapeutic drug monitoring (TDM). MATERIALS AND METHODS: This was a single-center, prospective study. Pregnant women with epilepsy on levetiracetam were enrolled after getting written informed consent from them. Serum trough levels of levetiracetam were estimated at all trimesters by high-performance liquid chromatography (HPLC). RESULTS: The study included 16 participants with mean ± standard deviation (SD) age of 27.75 ± 4 years. There were nine (56.2%) participants with generalized seizure disorder and seven (43.8%) participants of focal seizure disorder. Among 16 patients, 10 (62.5%) participants were on levetiracetam alone and six (37.5%) participants were on levetiracetam combined with other antiepileptic drugs. In a total of 48 trough samples, 45 sample concentrations were below the therapeutic range of 12-46 mg/l and three sample concentrations were within the therapeutic range. There was a statistically significant difference in the concentration-dose ratio (CDR) of levetiracetam between the third and first trimesters (P-value 0.018). CONCLUSION: There was a statistically significant difference in serum levetiracetam concentration between the third and first trimesters. A well-conducted, intensive pharmacokinetic sampling study in PWWE with a control group is needed in future to evaluate the whole pharmacokinetic profile of levetiracetam and to correlate the clinical outcome.

Assessment of the practical impact of adjusting beta-lactam dosages based on therapeutic drug monitoring in critically ill adult patients: a systematic review and meta-analysis of randomized clinical trials and observational studies.

An estimated 70% of critically ill patients receive antibiotics, most frequently beta-lactams. The pharmacokinetic properties of these substances in this patient population are poorly predictable. Therapeutic drug monitoring (TDM) is helpful in making personalized decisions in this field, but its overall impact as a clinical decision-supporting tool is debated. We aimed to evaluate the clinical implications of adjusting beta-lactam dosages based on TDM in the critically ill population by performing a systematic review and meta-analysis of available investigations. Randomized controlled trials and observational studies were retrieved by searching three major databases. The intervention group received TDM-guided beta-lactam treatment, that is, at least one dose reconsideration based on the result of the measurement of drug concentrations, while TDM-unadjusted dosing was employed in the comparison group. The outcomes were evaluated using forest plots with random-effects modeling and subgroup analysis. Eight eligible studies were identified, including 1044 patients in total. TDM-guided beta-lactam treatment was associated with improved clinical cure from infection [odds ratio (OR): 2.22 (95% confidence interval (CI): 1.78-2.76)] and microbiological eradication [OR: 1.72 (CI: 1.05-2.80)], as well as a lower probability of treatment failure [OR: 0.47 (CI: 0.36-0.62)], but the heterogeneity of studies was remarkably high, especially in terms of mortality (70%). The risk of bias was moderate. While the TDM-guided administration of beta-lactams to critically ill patients has a favorable impact, standardized study designs and larger sample sizes are required for developing evidence-based protocols in this field.

Total valproate versus free valproate in therapeutic drug monitoring for bipolar disorder: A cross-sectional study.

INTRODUCTION: The debate about observing total versus free serum valproate levels for therapeutic drug monitoring (TDM) has been unresolved for decades. This study was planned to assess the agreement between the total versus free valproate levels and the advantage of one method over the other in TDM. METHODS: The present cross-sectional study was done on 93 patients with bipolar disorder. The intraclass correlation coefficient, Bland Altman analysis, and Lin's concordance analysis were done to assess the agreement between the total and free valproate concentrations. Linear and polynomial models were constructed to evaluate the relation between the two measurements. Receiver operating characteristics analysis was done to compare the accuracy for differentiating remission from non-remission on Young's mania rating scale (YMRS). RESULTS: The intraclass correlation coefficient and Lin's concordance correlation coefficient were 0.491 (p = .002) and 0.055 (95% CI:0.037, 0.073), respectively. Bland Altman's analysis showed proportional bias. A polynomial model of second order was found to be the best fit for the prediction of free valproate from the data for total valproate, and 81.4% of the variability in free valproate could be explained when adjusted for albumin levels. The area under the curve for total valproate was 0.60 when compared to free valproate 0.56 for differentiating between remission and non-remission, but the comparison between the two ROC analyses was not statistically significant. CONCLUSION: Free valproate does not provide any added advantage over the total valproate levels; hence, total valproate levels may continue to be used as the marker for drug monitoring.

Therapeutic drug monitoring in inflammatory bowel disease patients on vedolizumab.

OBJECTIVE: We aimed to investigate whether vedolizumab (VDZ) levels were associated with inflammatory markers or clinical or endoscopic scoring in inflammatory bowel disease (IBD). METHODS: Besides demographic data, clinical scoring, endoscopic data, and laboratory markers of IBD patients treated with VDZ from 2015 to 2020 who had trough levels drawn on maintenance therapy were collected at baseline and at follow-up (after at least 8 weeks on VDZ therapy or after change in dose frequency). Low drug levels were defined as VDZ trough <20 µg/mL. RESULTS: We identified 89 patients with a mean age of 42.9 years. Of the 90 total trough levels drawn, 61.1% were low. Among patients on every 8 week (Q8 week) VDZ dosing, 81.5% had low troughs. After increasing dosing frequency to Q4 weeks, all patients showed improvement in VDZ levels, but 30.6% remained <20 µg/mL. Higher VDZ levels on Q8 week dosing were associated with higher albumin levels (P = 0.01). While higher VDZ levels on Q4 week dosing were associated with higher albumin (P = 0.02), lower erythrocyte sedimentation rate (P = 0.04) and higher likelihood of having mild disease or endoscopic remission (P = 0.01). No significant association was found between VDZ levels and clinical scoring, body mass index, hemoglobin, vitamin D or platelet levels on either Q8 or Q4 week dosing. CONCLUSIONS: Higher VDZ troughs were associated with higher albumin, mild endoscopic disease or endoscopic remission. Patients who continue to have low VDZ troughs despite Q4 week dosing may require a change in therapy.

Can Slow Personalized Titration Using C-Reactive Protein Monitoring Decrease the High Rates and Mortality of Clozapine-Associated Myocarditis Seen in Some Countries? A Call for Research.

PURPOSE/BACKGROUND: The hypothesis that slower personalized titration may prevent clozapine-associated myocarditis and decrease the disproportion incidence of 3% found in Australia was not described in a recent Australian article in this journal. METHODS: Six countries in addition to Australia have published information suggesting a similar incidence of clozapine-associated myocarditis. On September 19, 2023, PubMed searches were updated for articles from the United States, Korea, Japan, Canada, New Zealand, and Turkey. FINDINGS/RESULTS: An incidence of 3.5% (4/76) was found in a US hospital, but US experts were the first to propose that clozapine-associated myocarditis may be a hypersensitivity reaction associated with rapid titration and possibly preventable. Koreans and Japanese are of Asian ancestry and need lower minimum therapeutic doses for clozapine than patients of European ancestry. A 0.1% (2/1408) incidence of myocarditis during clozapine titration was found in a Korean hospital, but pneumonia incidence was 3.7% (52/1408). In 7 Japanese hospitals, 34% (37/110) of cases of clozapine-associated inflammation were found during faster titrations (based on the official Japanese titration) versus 13% (17/131) during slower titrations (based on the international titration guideline for average Asian patients). Recent limited studies from Canada, New Zealand, and Turkey suggest that slower personalized titration considering ancestry may help prevent clozapine-associated myocarditis. IMPLICATIONS/CONCLUSIONS: Other countries have very limited published data on clozapine-associated myocarditis. Based on a recent Australian case series and these non-Australian studies, the author proposes that Australia (and other countries) should use slow personalized titration for clozapine based on ancestry and c-reactive protein monitoring.