Long Term Exposure to High Variability of Tacrolimus Trough Levels and Exposure to Sub Therapeutic Drug Levels Predicts Worse Survival after Kidney Transplantation

2018 ◽  
Vol 102 ◽  
pp. S281
Author(s):  
Ruth Rahamimov ◽  
Avri Chagnac ◽  
Eytan Mor ◽  
Benjamin Fox ◽  
Benaya Rozen-Zvi
Keyword(s):  
Kidney Transplantation ◽  
High Variability ◽  
Therapeutic Drug ◽  
Drug Levels ◽  
Trough Levels

scholarly journals P01 An evaluation of vancomycin therapy in paediatric patients post guideline change

2020 ◽  
Vol 105 (9) ◽  
pp. e6.1-e6 ◽  
Author(s):  
Adedoyin Agbonin ◽  
Joanne Crook
Keyword(s):  
Adverse Effects ◽  
Renal Impairment ◽  
Therapeutic Drug ◽  
Drug Levels ◽  
Paediatric Patients ◽  
Patient Reported ◽  
The Right ◽  
Higher Doses ◽  
Trough Levels ◽  
Local Guideline

AimTo evaluate the prescribed dose of vancomycin as per local guideline and review the achieved therapeutic drug levels.MethodRetrospective data was collected from paediatric inpatients that were prescribed vancomycin for more than 24 hours during the audit period. Data was obtained from the Trust’s electronic prescribing system, LastWord. Measured standards included initial vancomycin dose, dose prescribed for renal impairment, time to first trough level and any required dose adjustments as per local guidance. The dose bands for each age group were1; birth - 6 months 15 mg/g 8 hourly; >6 months -12 months 20 mg/kg 8 hourly; >12 months – 12 years 25 mg/kg 8 hourly; >12 years 20 mg/kg 8 hourly. The number of patients achieving therapeutic vancomycin trough levels was recorded. Safety data was collected, including reported adverse effects, infusion related reactions and renal impairment. Renal impairment was defined as an increase in creatinine by 50%. Data was collected from April 2018 for 6 months. Relevant data with regards to patient demographics, dosing and drug levels were collected and analysed using Microsoft Excel.Results12 patients received 15 doses of vancomycin over 6 months. 67% of initial vancomycin doses were prescribed as per local guideline, 60% of therapeutic trough levels were taken at the right time and 71% of patients that were prescribed the correct dose and had levels taken at the right time achieved therapeutic trough levels. 12 patients required dose adjustments. One patient with renal impairment was not prescribed the recommended dose as per local guidance. One patient reported an infusion related reaction, which was overcome by increasing the infusion time. Two patients who received therapy for >7 days accumulated vancomycin and recorded high trough levels, with no adverse events. One patient reported an increase in creatinine by 50% over the treatment period.ConclusionsVancomycin has the potential to induce nephrotoxicity and ototoxicity when consistently at high serum drug levels. Due to its narrow therapeutic index, drug levels should be monitored to ensure the drug does not accumulate. The licensed dose and dose listed in the BNF for Children 2 3 has historically under dosed patients at our trust, leading to the risk of ineffective therapy and bacterial resistance. It is unclear from research what the optimal dose is for paediatric patients.More research is needed to determine the correct paediatric dose of vancomycin. Higher doses than currently recommended as per licence resulted in three quarters of patients achieving therapeutic levels, however 12 patients still required dose adjustment. No patients suffered irreversible adverse effects or toxicity, suggesting that higher doses are safe to use in the paediatric population. Further education is required for those involved in the prescribing, administering and monitoring of Vancomycin in paediatric patients to ensure its safe use. Additional monitoring is required for those receiving higher doses >7 days to prevent drug accumulation, alternatively a loading dose followed by lower maintenance dose may be a more suitable dosing regimen.ReferencesHughes S, Crook J, Ross J. Vancomycin intravenous dosing guideline - paediatrics. Chelsea and Westminster Hospital; 2017.Stockman C, Sammons H, Stakey E, et al. Unanswered Questions Regarding Optimal Pediatric Vancomycin Use. Therapeutic Drug Monitoring 2016; 38:491–420.National Institute for Health and Care Excellence. Vancomycin. Available from https://bnfc.nice.org.uk/drug/vancomycin.html [Accessed 10th Oct 2018]

scholarly journals Levels of Biosimilar Infliximab during and after Induction Treatment in Crohn’s Disease and Ulcerative Colitis—A Prospective Polish Population Study

2021 ◽  
Vol 10 (22) ◽  
pp. 5311
Author(s):  
Anna Pękala ◽  
Rafał Filip
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Induction Treatment ◽  
Therapeutic Drug ◽  
Induction Phase ◽  
Drug Levels ◽  
Trough Levels

Background: Primary lack or secondary loss of response to therapy with infliximab is a significant problem. This study aimed to evaluate the response to treatment in patients with Crohn’s disease (CD) and ulcerative colitis (UC) achieving therapeutic and sub-therapeutic trough levels of biosimilar infliximab (CT-P13). Results: A total of 65 patients (32 with CD and 33 with UC) were recruited. The overall response rate in both CD and UC patients exceeded 80%. There were no significant differences in treatment response and CT-P13 levels for patients with CD or UC. We did not find significant differences in the percentage of patients achieving drug levels of 3 μg/mL at week 6, 10, or 12; a significant decrease was observed at week 14. Up to 55.5% of patients with CD and 64.3% of patients with UC with sub-therapeutic CT-P13 levels at week 14 primarily responded to treatment. Conclusions: Intermediate measurements of drug levels at weeks 10 and 12 did not capture any pronounced decrease in infliximab concentrations below therapeutic levels in either group, thus suggesting no clinical usefulness. A significant percentage of patients primarily responded to treatment despite sub-therapeutic drug levels after the induction phase.

Evaluation of Therapeutic Drug Monitoring in a Long-Term Care Facility: A Pilot Project

1988 ◽  
Vol 22 (7-8) ◽  
pp. 594-596 ◽  
Author(s):  
Frank Pucino ◽  
Peggy J. Baumgart ◽  
Gordon L. Strommen ◽  
Inger-Lise Silbergleit ◽  
Dave Forbes ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Long Term Care ◽  
Care Facility ◽  
Therapeutic Drug ◽  
Term Care ◽  
Drug Levels ◽  
Long Term Care Facility ◽  
Drug Concentrations

The need for a therapeutic drug monitoring service was evaluated in a 150-bed long-term care facility. Thirty blood samples from 28 residents (mean age 87.9 years) were assayed to determine trough drug concentrations. All subjects were examined to determine pharmacodynamic effect. Pharmacokinetic consultations were written for serum drug concentrations outside accepted ranges. Fifty percent (15 of 30) of serum drug levels measured were subtherapeutic; the remaining levels were in the normal therapeutic range. Based on this sample data, it could be concluded that a minimum of 32 percent and as many as 68 percent of serum drug levels would be subtherapeutic following drug analysis in similar nursing home populations. Of 12 consultations, recommendations for seven (58 percent) were accepted by the subject's primary care physicians. Four of the consultations (33 percent) resulted in dosage modifications. These results support the need for further study.

scholarly journals Comparing Predictions of a PBPK Model for Cyclosporine With Drug Levels From Therapeutic Drug Monitoring

2021 ◽  
Vol 12 ◽  
Author(s):  
Sonja E. Zapke ◽  
Stefan Willmann ◽  
Scott-Oliver Grebe ◽  
Kristin Menke ◽  
Petra A. Thürmann ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Pbpk Model ◽  
Clinical Population ◽  
Pbpk Modeling ◽  
Additional Patient ◽  
Therapeutic Drug ◽  
Model Parameters ◽  
Drug Levels ◽  
Trough Levels

This study compared simulations of a physiologically based pharmacokinetic (PBPK) model implemented for cyclosporine with drug levels from therapeutic drug monitoring to evaluate the predictive performance of a PBPK model in a clinical population. Based on a literature search model parameters were determined. After calibrating the model using the pharmacokinetic profiles of healthy volunteers, 356 cyclosporine trough levels of 32 renal transplant outpatients were predicted based on their biometric parameters. Model performance was assessed by calculating absolute and relative deviations of predicted and observed trough levels. The median absolute deviation was 6 ng/ml (interquartile range: 30 to 31 ng/ml, minimum = −379 ng/ml, maximum = 139 ng/ml). 86% of predicted cyclosporine trough levels deviated less than twofold from observed values. The high intra-individual variability of observed cyclosporine levels was not fully covered by the PBPK model. Perspectively, consideration of clinical and additional patient-related factors may improve the model’s performance. In summary, the current study has shown that PBPK modeling may offer valuable contributions for pharmacokinetic research in clinical drug therapy.

scholarly journals Intra-patient variability in tacrolimus trough levels over 2 years affects long-term allograft outcomes of kidney transplantation

2021 ◽  
Vol 35 (1) ◽  
pp. S88-S88
Author(s):  
Yohan Park ◽  
Hanbi Lee ◽  
Sang Hun Eum ◽  
Hyung Duk Kim ◽  
Eun Jeong Ko ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Trough Levels

scholarly journals Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis

2020 ◽  
Vol 65 (1) ◽  
pp. e01511-20
Author(s):  
Chris Kosmidis ◽  
Akan Otu ◽  
Caroline B. Moore ◽  
Malcolm D. Richardson ◽  
Riina Rautemaa-Richardson
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Adverse Events ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Pulmonary Aspergillosis ◽  
Drug Levels ◽  
Long Term Treatment ◽  
Daily Dose ◽  
Chronic Pulmonary Aspergillosis

ABSTRACTIsavuconazole is the newest triazole antifungal, and it displays a favorable pharmacokinetic and safety profile. Less is known about its long-term use in immunocompetent hosts. We performed a retrospective service evaluation of isavuconazole therapeutic drug monitoring in patients with chronic pulmonary aspergillosis. Adverse events (AEs) and dose adjustments made during routine clinical practice were recorded, and AEs were classified based on Common Terminology Criteria for Adverse Events v5.0. Forty-five patients (mean age, 64 years) had 285 isavuconazole blood drug levels measured (mean level, 4.1 mg/liter). A total of 117 measurements (41%) were performed on patients on a 100-mg daily dose instead of 200 mg, and all had blood levels of >1 mg/liter. Age (P = 0.012) and a daily dose of 200 mg versus 100 mg (P = 0.02) were independent predictors of levels of >6 mg/liter. AEs were recorded for 25 patients (56%). The mean drug level at the first measurement was 5.5 ± 2 mg/liter for patients reporting AEs, compared with 4.2 ± 1.7 mg/liter for those not reporting AEs (P = 0.032). The cutoff threshold best predictive of an AE was 4.6 mg/liter (area under the concentration-time curve, 0.710). Sixteen patients (36%) discontinued isavuconazole therapy due to AEs. Twenty-six patients (58%) continued on isavuconazole beyond 6 months. Asthma (P = 0.022) and a daily dose of 200 mg versus 100 mg (P = 0.048) were associated with AEs of grade 2 or higher. A reduced daily dose (100 mg versus 200 mg) of isavuconazole resulted in satisfactory drug levels in a substantial number of patients; it was better tolerated and enabled continuation of therapy for prolonged periods.

scholarly journals Intrapatient Variability in Tacrolimus Trough Levels Over 2 Years Affects Long-Term Allograft Outcomes of Kidney Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yohan Park ◽  
Hanbi Lee ◽  
Sang Hun Eum ◽  
Hyung Duk Kim ◽  
Eun Jeong Ko ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Trough Level ◽  
First Year ◽  
High Group ◽  
Post Transplant ◽  
Intrapatient Variability ◽  
Allograft Loss ◽  
The Impact ◽  
Trough Levels

This study aimed to determine the impact of tacrolimus (TAC) trough level (C0) intrapatient variability (IPV) over a period of 2 years after kidney transplantation (KT) on allograft outcomes. In total, 1,143 patients with low immunologic risk were enrolled. The time-weighted coefficient variability (TWCV) of TAC-C0 was calculated, and patients were divided into tertile groups (T1: < 24.6%, T2: 24.6%–33.7%, T3: ≥ 33.7%) according to TAC-C0-TWCV up to post-transplant 1st year. They were classified into the low/low, low/high, high/low, and high/high groups based on a TAC-C0-TWCV value of 33.7% during post-transplant 0–1st and 1st–2nd years. The allograft outcomes among the three tertile and four TAC-C0-TWCV groups were compared. The T3 group had the highest rate of death-censored allograft loss (DCGL), and T3 was considered an independent risk factor for DCGL. The low/low group had the lowest and the high/high group had the highest risk for DCGL. Moreover, patients with a mean TAC-C0 of ≥5 ng/ml in the high/high group were at the highest risk for DCGL. Thus, TAC-IPV can significantly affect allograft outcomes even with a high mean TAC-C0. Furthermore, to improve allograft outcomes, a low TAC-IPV should be maintained even after the first year of KT.

scholarly journals Therapeutic Drug Monitoring to Guide Clinical Decision Making in Inflammatory Bowel Disease Patients with Loss of Response to Anti-TNF: A Delphi Technique-Based Consensus

Digestion ◽  
2019 ◽  
Vol 101 (6) ◽  
pp. 683-691 ◽  
Author(s):  
Thomas Greuter ◽  
Michel H. Maillard ◽  
Pascal Juillerat ◽  
Pierre Michetti ◽  
Frank Seibold ◽  
...  
Keyword(s):  
Decision Making ◽  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Therapeutic Drug ◽  
Drug Levels ◽  
Loss Of Response ◽  
Antidrug Antibody ◽  
Antibody Titers ◽  
Inflammatory Bowel ◽  
Trough Levels

<b><i>Background:</i></b> Loss of response is frequently encountered in patients with inflammatory bowel disease (IBD) treated with antitumor necrosis factor (TNF) agents. Therapeutic drug monitoring (TDM) and antidrug antibody measurement are increasingly used in this setting. <b><i>Methods:</i></b> To establish a consensus on the use of TDM in the context of loss of response to anti-TNFs, we performed a vote using a Delphi-style process followed by an expert panel discussion among 8 IBD specialists practicing in Switzerland, Europe. Statements were rated on an even Likert-scale ranging from 1 (strong disagreement) to 4 (strong agreement), based on expert opinion and the available literature. <b><i>Results:</i></b> The experts agreed on the following statements: (i) loss of response is associated with inadequate drug levels in both Crohn’s disease and ulcerative colitis; (ii) best timepoint for measuring drug levels is prior to the next application (= trough levels) with different thresholds for anti-TNF agents (infliximab 5 μg/mL, adalimumab 8 μg/mL, certolizumab pegol 10 μg/mL); (iii) antidrug antibodies are predictive for loss of response; and (iv) antidrug-antibody titers and drug trough levels are key determinants in the treatment algorithm. Data about non-anti-TNF biologics were considered too limited to propose recommendations. <b><i>Conclusion:</i></b> A Delphi-style consensus among 8 IBD experts shows that TDM and measurement of antidrug-antibody titers are useful in the context of loss of response to anti-TNF. Optimal cutoff levels depend on the type of anti-TNF. These values are critical in the decision making process. More studies are needed to address the value of such measurements for non-anti-TNF biologics.

scholarly journals Tacrolimus Therapeutic Drug Monitoring in Kidney Transplant Patients Before and After Pharmacist Post-transplant Consults

2021 ◽  
Vol 12 (3) ◽  
pp. 18
Author(s):  
Gabriella Massoglia ◽  
Michael J. Schuh
Keyword(s):  
Kidney Transplant ◽  
Clinical Pharmacist ◽  
Therapeutic Drug ◽  
Improvement Project ◽  
Drug Levels ◽  
Post Transplant ◽  
Transplant Patients ◽  
Number Of Patients ◽  
Kidney Transplant Patients ◽  
Trough Levels

Objectives: This quality improvement project sought to determine if clinical pharmacist office visits, or consults, had an impact on therapeutic tacrolimus levels in patients after kidney transplant through analysis of tacrolimus serum concentrations before versus after a pharmacist visit. Methods: A retrospective chart review was conducted for all patients that attended a clinical pharmacist office visit, also known as a consult, after kidney transplantation for a four month period. Pharmacists during the post-transplant consult reviewed adherence but also educated patients in detail about timing and logging of tacrolimus dosing, dosing with regard to labs to assure trough dosing, dosing with or without food in the stomach, what to do with a dose is taken late or if a dose is missed and foods, herbal supplements to avoid that may inhibit CYP3A4 to elevate tacrolimus levels. Results: After the post-transplant visit with a clinical pharmacist there was a 46% increase in the number of tacrolimus trough levels in therapeutic range versus before the pharmacist visit. Sixty-four percent of kidney transplant patients experienced an increase in the number of therapeutic drug levels in range after the pharmacist visit versus before the pharmacist visit. Conclusions: An increase in the quantity of therapeutic tacrolimus trough levels and the number of patients with therapeutic drug levels in range was observed after patients received pharmacist provided medication education post-transplant with emphasis on proper immunosuppressant medication administration, adherence and potential drug and food interactions. This finding demonstrates the importance of pharmacist clinical services in producing improved therapeutic drug levels in post-transplant kidney patients.

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