Therapeutic Drug Monitoring Requests Research Articles

Optimizing vancomycin therapeutic drug monitoring compliance in pediatric oncology: towards personalized medication management.

Aim: Vancomycin, a crucial treatment for Gram-positive bacteria, necessitates therapeutic drug monitoring (TDM) to prevent treatment failures. We investigated the healthcare professional's compliance toward TDM of vancomycin recommendations and follow-up levels. Materials & methods: We collected data from 485 patients who received vancomycin in the Children's Cancer Hospital Egypt 57357 medical records system (Cerner) over 4 months, from January to April 2020. Results: Our data shows that only 54% of patients had TDM requests from healthcare professionals for the total patients who received vancomycin treatment. The healthcare professionals' compliance with the recommendations was 91.7%, while the follow-up levels were 66.7%. Conclusion: While overall adherence to recommendations is strong, enhancing compliance with follow-up levels remains a priority for improvement.

Therapeutic Drug Monitoring Characteristics in a City Hospital for a Year.

Therapeutic drug monitoring (TDM) involves the measurement of drug concentrations in serum, plasma, whole blood, or other biologic fluids. This study focused on evaluating the TDM requests of a city hospital over a period of one year, retrospectively. The study retrospectively analyzed TDM requests for carbamazepine, cyclosporine-A, digoxin (DIGOX), lithium (LITH), methotrexate (MTX), phenitoin, tacrolimus, and valproic acid (VALP) from June 1, 2022, to June 1, 2023. Parameters such as the age and the gender of patients, the requesting departments, the measurement results, and the turnaround time (TAT) were assessed. Drug concentrations below the reference values were classified as subtherapeutic, whereas concentrations above the reference values were considered supratherapeutic. In total, 10,913 drug concentration measurement records were analyzed. The gender distribution was 51.6% male and 48.4% female. Pediatric samples comprised 6.2% and elderly samples 8.6% of the total. Notably, DIGOX, LITH, and VALP levels showed a significant correlation with age (p = < 0.0001, p = < 0.0001, and p = 0.0002, respectively). TAT was maintained at 360 minutes (6 hours) for all tests. The study found significant correlations between age and DIGOX, LITH, and VALP levels. TDM plays a critical role in the elderly population, necessitating careful management of these drugs.

Clinical impact of therapeutic drug monitoring for newer anti-seizure medications in patients with epilepsy: A real-world observation study

BackgroundThe clinical value of therapeutic drug monitoring (TDM) for newer anti-seizure medications (ASMs) remains uncertain. This study aimed to assess the impact of newer ASM TDM on clinical decision making in patients with epilepsy. MethodsWe retrospectively identified all plasma requests for newer ASM level measurement as part of routine clinical management in the outpatient departments of seven medical institutes across Taiwan between September 2016 and May 2019. Data collected from reviewed medical records included clinical and medication details, indications for TDM requests, test results, interpretation, and impact on patient management. ResultsA total of 682 visits with 1051 plasma samples were included. The most frequently analyzed ASMs were levetiracetam (36.1%), oxcarbazepine (18.4%), and lamotrigine (12.0%). Reasons for TDM included poorly controlled seizures (55.3%), concerns about drug-drug interactions (12.3%), and suspicion of drug overdose (10.6%). 68.8% of samples were within the orienting therapeutic range, even for patients with poorly controlled seizures. TDM for non-adherence concerns showed 54.3% below the orienting therapeutic range, while ASM-related adverse events assessment only 8.9% showed levels exceeding the orienting therapeutic range. Following TDM results, 64.2% of cases had medication adjustments, mainly dosage increases. Overall, 55.9% of newer ASM TDM visits showed improved outcomes, including reduced seizures (47.5%) and fewer ASM-related side effects (8.4%). ConclusionsThese findings suggest that appropriate utilization of TDM for newer ASMs provides clinical benefits in adjunct to complement clinical decision making in the management of epilepsy patients in a real-world clinical setting.

Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for Therapeutic Drug Monitoring in patients with Inflammatory Bowel Disease.

Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blood sampling can be undertaken by patients at home and samples returned by post to central laboratories. We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low volume Patient-led Remote IntraCapillary pharmacoKinetic Sampling [fingerPRICKS] compared to conventional venepuncture. We undertook a cross-sectional blood sampling methods comparison study and compared sample types using linear regression models. Drug and antidrug antibody levels were measured using standard ELISAs. Acceptability was assessed using a purpose-designed questionnaire. Therapeutic drug monitoring requests for adalimumab (96.5 [70.5-106] per week to 52 [33.5-57.0], p < 0.001) but not infliximab (184.5 [161.2-214.2] to 161 [135-197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding 6 months. Fingerprick sampling was equivalent to conventional venepuncture for adalimumab, infliximab, vedolizumab and ustekinumab drug, and anti-adalimumab and anti-infliximab antibody levels. The median [interquartile range] volume of serum obtained using intracapillary sampling was 195 µL [130-210]. More than 87% [90/103] of patients agreed that intracapillary testing was easy and 69% [71/103] preferred it to conventional venepuncture. In routine care, 75.3% [58/77] of patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.

Rapid and Simple Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) Method for Simultaneous Quantifications of Triazole Antifungals in Human Serum.

To develop and validate a one-step, rapid and simple reversed-phase high-performance liquid chromatography (HPLC)-based protocol for the simultaneous measurement of voriconazole (VCZ), posaconazole (POSA), itraconazole (ITC) in serum/plasma. Calibration standards (CS) and quality control samples were prepared in drug-free serum by spiking with the triazoles at different concentrations. HPLC was performed with C18 column, isocratic mobile phase after extraction with cold acetonitrile. The standardized method was tested in 2693 patients' serum/plasma samples. Linearity of CS for ITC, VCZ and POSA was proportional to the nominal concentration (correlation coefficient > 0.999). Limit of detection (mg/L) for ITC, VCZ and POSA was 0.25, 0.25 and 0.125, respectively. The lower limit of quantification (mg/L) for ITC, VCZ and POSA was 0.5, 0.5 and 0.25, respectively. Precision and accuracy were in acceptable range with 100% average percentage recovery. No interferences from endogenous substances and other antimicrobial compounds were noted. In clinical samples, the therapeutic range achieved for VCZ was 39.9%. Whereas, 61.1% and 44% of samples with ITC and POSA, respectively, were in the sub-therapeutic range. We developed a rapid and simple HPLC method to quantify common triazoles in a single chromatographic run allowing simultaneous measurement of different antifungals in a small volume of serum/plasma. Thus, therapeutic drug monitoring requests can be processed in one run without changing the protocol parameters, column or column conditioning thereby improving turnaround time.

Supra-therapeutic Linezolid Trough Concentrations in Elderly Patients: A Call for Action?

According to the drug label, linezolid dosage adjustments are not needed in geriatric patients. Nevertheless, clinical evidence suggests that elderly patients may benefit from the use of reduced linezolid doses to limit drug overexposure. Here, we aimed to describe the results of the last 5 years of therapeutic drug monitoring of linezolid in our institution with a special focus on elderly patients. Linezolid therapeutic drug monitoring requests collected between January 2016 and June 2020 were considered. Linezolid trough concentrations were considered both as a continuous variable and as a categorical variable, clustering data according to the therapeutic range proposed by available literature (< 2, 2-8, and > 8 mg/L, respectively). Patients' age and sex were considered as categorical variables. Comparisons of linezolid trough concentrations between groups of patients stratified according to age were performed using an analysis of variance; comparisons in the frequency distributions were performed using the chi-squared test. From 2016 to 2020, we collected 3250 linezolid TDM requests. A highly significant, progressive increment in the linezolid trough concentrations was observed moving from patients aged < 50 years (5.8 ± 5.6 mg/L) to those aged > 90 years (16.6 ± 10.0 mg/L), with an overall increment of 30% per decade of age. Nearly 30%, 50%, and 65% of patients aged < 65 years, 65-80 years, and > 80 years, respectively, had supra-therapeutic linezolid trough concentrations at the first therapeutic drug monitoring assessment. This trend did not change significantly moving from 2016 to 2020. Elderly patients given linezolid at the conventional 600-mg twice-daily dose might be at a high risk of being overexposed to treatment, eventually increasing their risk to experience drug-related hematological toxicity. Reduced linezolid dosing schemes should be potentially considered in elderly patients at a low risk of treatment failure, ideally guided by therapeutic drug monitoring.

A survey of therapeutic drug monitoring in a teaching hospital.

ObjectivesTherapeutic drug monitoring (TDM) is one of the tools that aim to improve and ensure the best therapeutic effects while avoiding drug toxicity. This study aimed to identify the clinical utilization and application of TDM at a major teaching hospital in Jeddah.MethodsA cross sectional survey of the clinical utilization and application of TDM at King Abdulaziz University Teaching Hospital across nurses in medical, surgical, pediatric, and intensive care units. The sample size (n = 130) represented 30% of the nursing population. The collection of questionnaires started on the 31st of January 2019 and was completed by the 10th of March 2019.ResultsThe indication to use TDM was well-known to respondents. However, only 64% of respondents reported collection and measuring of the correct drug levels at a precise sampling time with no specific protocols being followed for each drug. Moreover, only 53% reported that the drug levels were being re-measured and adequately monitored for the right indication and proper sampling time. Regarding the presence of clinical pharmacists, 70% of the respondents indicated that no clinical pharmacist worked in their department.ConclusionResults demonstrate that appropriate sampling time was not used for the majority of monitored drugs. In the absence of a TDM request form, this finding probably indicates the lack of national or local TDM guidelines. In conclusion, TDM services, which include standardized forms, references, and an active clinical pharmacist will likely improve the application of TDM.

Therapeutic Drug Monitoring Characteristics in a Tertiary University Hospital in 2019.

IntroductionTherapeutic drug monitoring (TDM) is defined as measuring drug concentration in a biological sample to optimize pharmacotherapy. This study aims to evaluate TDM requests in a tertiary university hospital retrospectively.Materials and methodsTDM requests were evaluated retrospectively for lithium, valproic acid, carbamazepine, and digoxin in 2019. The age and gender of the patient, requesting department, and measurement results were evaluated. Lower levels than the reference values were considered as subtherapeutic, while levels higher than the reference were considered as toxic.Results A total of 415 drug level measurement records were found. The pediatric age sample ratio was 13.7%, and the elderly age sample ratio was 11.8%. When all samples were evaluated according to the relevant laboratory cut-off values, 72.8% of samples were within the therapeutic level range, 21.9% of samples were subtherapeutic, and 5.3% were toxic. The pediatric age group had a higher ratio of toxic levels for the four drugs studied (54.5%).ConclusionsTests for lithium, valproic acid, carbamazepine, and digoxin would not be considered sufficient for TDM. Multidisciplinary teamwork might be appropriate for further implementation and interpretation of TDM.

Vancomycin therapeutic drug monitoring service quality indices and clinical effectiveness outcomes: A retrospective cohort and clinical audit

AbstractIntroductionVancomycin is commonly used for the treatment of complicated infections caused by methicillin‐resistant Staphylococcus aureus. The impact of vancomycin therapeutic drug monitoring (TDM) quality indices on clinical outcomes has not been previously explored.ObjectivesThis study aims to relate routine vancomycin TDM service quality indices to clinical effectiveness outcomes and to develop a pragmatic vancomycin‐specific TDM quality assessment tool that can be used in quality audits.MethodsA retrospective chart review was conducted on adult non‐dialysis vancomycin TDM records documented between January 2014 and October 2016 in three tertiary care hospitals under Hamad Medical Corporation (HMC) in Qatar. Evidence‐based criteria and pilot‐testing were applied to develop a quality assessment tool. The appropriateness of vancomycin TDM service and clinical outcomes were simultaneously evaluated.ResultsA 13‐criterion vancomycin TDM quality assessment tool was developed and used to evaluate 208 TDM records involving 99 patients. The indications for TDM requests were judged appropriate in 77.4% (n = 161) of the records. However, most of the blood samples were deemed to be incorrectly timed (70.7%, n = 147). Inappropriate vancomycin TDM practices compared with appropriate practices were associated with lower therapeutic cure (47.3% vs 75%, P‐value = .009).ConclusionsVancomycin TDM requests were justified at HMC. However, inappropriate practices were associated with suboptimal clinical outcomes, signifying the importance of routine quality audits using rigorous evaluation tools. The developed tool can be used to determine setting‐specific deficiencies in routine vancomycin TDM practices.

Pediatric Antiretroviral Therapeutic Drug Monitoring: A Five and a Half Year Experience from a South African Tertiary Hospital.

Antiretroviral therapeutic drug monitoring (TDM) is not routinely used in the management of human immunodeficiency virus, but may be useful in pediatric patients who are prone to altered pharmacokinetics. Data on the routine use of antiretroviral TDM in pediatrics are sparse especially data from sub-Saharan Africa. We retrospectively reviewed the antiretroviral TDM indications at Tygerberg Children's Hospital, identified pediatric patients who had antiretroviral TDM requests from January 2012 until June 2017 and reviewed their clinical records. Fifty-nine patients were identified who presented with 64 clinical problems for which TDM was requested. TDM was requested for lopinavir, efavirenz and nevirapine in 83% (53/64), 14% (9/64) and 3% (2/64) of clinical problems, respectively. Lopinavir was mostly requested in patients when adherence measures did not correlate with the clinical picture, suspected non-adherence, lopinavir-rifampicin interactions and for neonatal safety monitoring. Efavirenz was requested when toxicity was suspected and nevirapine in patients receiving rifampicin. Lopinavir TDM confirmed non-adherence in 25% (4/16) of cases when adherence measures did not correlate with the clinical picture and in 43% (3/7) of cases when non-adherence was suspected by the clinician. Efavirenz TDM confirmed toxicity in 100% (6/6) of patients. Lopinavir TDM was mostly requested when adherence measures did not correlate with the clinical picture, when rifampicin was co-administered and for perinatal safety monitoring. Lopinavir TDM excluded pharmacokinetic reasons for failure in patients failing treatment when lopinavir dosing was supervised. Efavirenz TDM was requested for suspected toxicity with a 100% positive predictive value.

Monitoring Protein-Unbound Valproic Acid Serum Concentrations in Clinical Practice.

Valproic acid (VPA) is an effective antiepileptic drug and mood stabilizer. A key characteristic of VPA is its high and saturable protein binding at higher concentrations. Although the unbound concentration of VPA is responsible for its pharmacological activity, total drug concentrations are monitored in routine clinical practice. Therapeutic drug monitoring (TDM) of unbound VPA is recommended for specific clinical situations. The goal of this study was to evaluate TDM requests for unbound VPA in clinical practice. All TDM requests at our laboratory for unbound VPA in 2014 and 2015 were evaluated retrospectively. In patients with potentially toxic unbound VPA concentrations (ie, >12 mg/L), we evaluated whether toxicity was noted and whether the dose adjustment advice was followed. Total and unbound VPA concentrations were measured by means of a validated immunoassay. A total of 273 unbound VPA serum concentrations in 132 different patients were analyzed. The main reasons for unbound VPA TDM were decreased renal function (34%) and a low serum albumin (27%). The median (range) unbound VPA concentration was 9.8 (2.5-47.6) mg/L. In 49 patients (37%), the initial unbound VPA concentration was above the threshold of 12 mg/L, potentially resulting in toxicity. Only 6 of these 49 patients had elevated total VPA concentrations. Clinical toxicity was noted in 38 of the 49 patients (77.6%) with elevated unbound VPA concentrations. Toxicities included drowsiness (n = 26), decreased consciousness (n = 4), rigidity (n = 2), and confusion (n = 2). In 36 of the 38 patients with elevated unbound VPA concentrations and clinical toxicity, a dose reduction was applied. In 27 of 36 patients who had their dose reduced, dose reduction was associated with improvement or resolution of VPA toxicity. TDM of unbound VPA is an important tool to manage VPA therapy in selected, vulnerable patients.

First line anti-tuberculosis induced hepatotoxicity: incidence and risk factors.

In our days, tuberculosis, whet ever its localization, became a curable disease. The cornerstone is a 6 month course of isoniazid, rifampicine and pyrazinamide. All of the three first line antituberculosis drugs may induce hepatic damage which may have negative consequences for treatment outcome. Several risk factors were associated with the development of antituberculosis- drug-induced hepatotoxicity (ATDH). A retrospective study was conducted from July 2014 to March 2015 regarding all therapeutic drug-monitoring requests sent to the Laboratory of Poison Control and Pharmacovigilance Centre of Morocco. 142 patients diagnosed with active tuberculosis were included in study. Plasma peak levels of isoniazid, rifampicin and pyrazinamide were analyzed in plasma samples after 2 to 3 hours of administration of anti-tuberculosis treatment. Logistic regression was used to identify the ATDH risk factors. The incidence of ATDH was found 24.6% (35 patients out of 142). Intergroup differences in the plasma levels were statistically significant for isoniazid (p=0.036). ATDH was found to be associated with combined form of anti-TB drugs (p=0.002, COR=13.1, AOR= 13.5) and plasma concentration of INH superior to 2mg/l (p=0.045, COR=1.3, AOR= 1.4).age, gender, alcohol intake and smoking status were not significantly associated with ATDH. The finding of 24.6% incidence of hepatotoxicity is extremely high. Many factors can be associated with the development of ATDH such as genetic factors, combined forms of treatment and plasma peak levels.

Inflammation and psychotropic drugs: the relationship between C-reactive protein and antipsychotic drug levels.

In psychiatric clinical practice, there is a need to identify psychotropic drugs whose metabolisms are prone to be altered with increased inflammatory activity in an individual patient. The aim of this study was to find out whether elevated serum levels (≥5mg/l) of C-reactive protein (CRP), an established laboratory marker of infection and inflammation, are associated with increased serum concentrations of the atypical antipsychotic drugs clozapine, quetiapine, and risperidone. Therapeutic drug monitoring request forms of patients whose antipsychotic drug concentrations had been measured under conditions of normal (<5mg/l) and pathological (>5mg/l) levels of C-reactive protein were retrospectively screened. The serum concentrations in relation to the daily doses [concentration per dose (C/D) (ng/mL/mg)] and the metabolic ratios [ratio of concentrations (metabolite/drug)] were compared intraindividually by the Wilcoxon signed rank test. To the study effects of the intensity of infections on drug concentrations, C-reactive protein and C/D levels were submitted to Spearman's correlation analysis. Elevated levels of C-reactive protein were found in 105 patients. They were significantly associated with elevated values in C/D for clozapine (n = 33, P < 0.01) and risperidone (n = 40, P < 0.01). A trend for an increase was found for quetiapine (n = 32, P = 0.05). Median increases were 48.0% (clozapine), 11.9% (quetiapine), and 24.2% (active moiety of risperidone), respectively. In patients who exhibit signs of inflammation or infection with increased C-reactive protein values during psychopharmacological treatment, especially under clozapine and risperidone, therapeutic drug monitoring is recommendable in order to minimize the risk of intoxications due to elevated drug concentrations.

Impact of the introduction of real-time therapeutic drug monitoring on empirical doses of carbapenems in critically ill burn patients

PurposeAdequate empirical antibiotic dose selection for critically ill burn patients is difficult due to extreme variability in drug pharmacokinetics. Therapeutic drug monitoring (TDM) may aid antibiotic prescription and implementation of initial empirical antimicrobial dosage recommendations. This study evaluated how gradual TDM introduction altered empirical dosages of meropenem and imipenem/cilastatin in our burn ICU. MethodsImipenem/cilastatin and meropenem use and daily empirical dosage at a five-bed burn ICU were analyzed retrospectively. Data for all burn admissions between 2001 and 2011 were extracted from the hospital's computerized information system. For each patient receiving a carbapenem, episodes of infection were reviewed and scored according to predefined criteria. Carbapenem trough serum levels were characterized. Prior to May 2007, TDM was available only by special request. Real-time carbapenem TDM was introduced in June 2007; it was initially available weekly and has been available 4 days a week since 2010. ResultsOf 365 patients, 229 (63%) received antibiotics (109 received carbapenems). Of 23 TDM determinations for imipenem/cilastatin, none exceeded the predefined upper limit and 11 (47.8%) were insufficient; the number of TDM requests was correlated with daily dose (r=0.7). Similar numbers of inappropriate meropenem trough levels (30.4%) were below and above the upper limit. Real-time TDM introduction increased the empirical dose of imipenem/cilastatin, but not meropenem. ConclusionsReal-time carbapenem TDM availability significantly altered the empirical daily dosage of imipenem/cilastatin at our burn ICU. Further studies are needed to evaluate the individual impact of TDM-based antibiotic adjustment on infection outcomes in these patients.

Side effects related to potentially inappropriate medications in elderly psychiatric patients under everyday pharmacotherapy

Potentially inappropriate medication (PIM) is suggested to give rise to adverse drug events. To study this suggestion for elderly psychiatric patients, an observational analysis related prescription of PRISCUS PIMs and drug-induced side effects in old aged (≥65 years) psychiatric inpatients and outpatients under conditions of everyday pharmacotherapy. Request forms from a therapeutic drug monitoring (TDM) survey and medical files were screened for medication to identify PIMs of the PRISCUS list and assessed using the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale. From 914 TDM request forms, data were available for 168 patients (64.3 % female). Patients (mean ± SD age 73.0 ± 5.5 years) received by mean 6.4 ± 3.9 drugs per day. More than half of them (53.0 %, n = 89) had at least one PIM, inpatients 0.9 ± 0.8 and outpatients 0.5 ± 0.7. Predominant PIMs were hypnotic drugs (69 %) in inpatients and antipsychotic drugs (35.6 %) in outpatients. The number of PIMs correlated with the total number of drugs administered per day (Spearman correlation coefficient 0.225, p < 0.01, CI 95 %). Side effects were documented for 106 patients (63 %). Severity of side effects did not correlate significantly (p > 0.05) with number of PIMs. However, only 6 of 77 patients who took no PRISCUS PIMs but 2 of 3 patients who took 3 PRISCUS PIMs exhibited severe side effects. Though the prevalence for PIMs and side effects was high in old aged psychiatric inpatients and outpatients, PIMs could not be identified as major determinants of overall unwanted side effects. Nevertheless, prescription of PIMs should be minimized, especially of hypnotic drugs, to improve safety.

English

In epilepsy, therapeutic drug monitoring (TDM) could aid in individualizing dosage regimen and ascertaining compliance on anti-epileptic drugs (AEDs). The aim of this study was to survey the requests for TDM of AEDs to determine drugs involved, observed concentrations, reasons for requests and action undertaken. TDM requests for AEDs were surveyed at a university hospital in Oman from January 2006 to December 2009. A total of 151 patients with 354 TDM requests were collected. These requests were for valproic acid (46.9%), phenytoin (26.8%), carbamazepine (25.4%) and phenobarbital (0.8%). 50, 37 and 13% of all reported concentrations were below, within and above therapeutic range, respectively. For majority of the subjects (70%), there were no clear reasons for plasma concentrations to lie outside the therapeutic range. No change in the drug therapy/dosing was required subsequent to the TDM reports in 42.7% of the cases. Emergency department was the main unit requesting TDM (63.8%) and TDM was mostly indicated for an increase in the seizures frequency on the same day (62.7%). This study provides an overview of the specific requests for TDM of AEDs in routine clinical practice which might help in auditing and improving this service for optimal utilization. Key words: Antiepileptic drugs, therapeutic drug monitoring, epilepsy, plasma.

Utilization patterns of antiepileptic drugs among adult epileptic patients at a tertiary hospital in Oman

To describe utilization patterns of antiepileptic drugs (AEDs) among adult epileptic patients at a tertiary hospital in Oman. Data were collected retrospectively from January 2006 to December 2009. The study included all adult (>18 years) epileptic patients on AEDs and followed up at a neurology clinic at Sultan Qaboos University Hospital in Oman. All reported therapeutic drug monitoring (TDM) requests for serum AED concentrations were also collected. Institutional ethical approval was sought and obtained. The study included a total of 372 patients with a mean age of 34 ± 15 years. Monotherapy AEDs accounted for 53% of the prescriptions, whereas polytherapy with two or three AED combinations accounted for 27% and 20% respectively. The most frequently prescribed AED was sodium valproate (27%) followed by carbamazepine (23%). The commonly prescribed AED combinations were sodium valproate with clonazepam (12%) followed by sodium valproate with lamotrigine (12%). Evaluation of 574 TDM requests for three AEDs showed that 57% of carbamazepine, 78% of phenytoin and 54% of valproic acid requests were either above or below the recommended therapeutic threshold. Most of these requests were ordered from the hospital's emergency department for suspected insufficient serum concentrations. Antiepileptic drug monotherapy is still the most frequently employed therapeutic strategy in adult patients with epilepsy in keeping with the standard therapeutic guidelines. Sodium valproate is commonly used for different types of seizures reflecting its wide spectrum of anticonvulsant potential. Newer AED utilizations are becoming increasingly popular in our subjects particularly as add-on with other standard AEDs.

Practices Associated with Serum Antiepileptic Drug Level Monitoring at a Pediatric Neurology Clinic

Objectives: To assess the practices associated with the application of therapeutic drug monitoring (TDM) for antiepileptic drugs (AEDs) in the management of children with structural–metabolic epilepsy. Methods: It was a retrospective chart review and included children aged ≥2 years old with structural–metabolic epilepsy, treated with AEDs, and received TDM. The data were extracted from the medical records. Results: Thirty-two patients were identified with 50 TDM assays. In two thirds of the assays, “check level” and “recheck level” were the reasons behind the requesting of serum level monitoring of AEDs. Knowledge of serum AED levels led to alterations in the management in 60% of the assays. Thirty-two (76%) pediatrician’s actions were consistent with the recommendation of TDM pharmacist. Forty-nine (98%) levels were appropriately indicated. In relation to the appropriateness of sampling time, 9 (18%) levels were not assessed due to missing data. Twenty-seven (54%) levels were appropriately sampled. Conclusions: More studies should be designed to improve the component of the current TDM request form, especially in the reason section. By the same token, the number of pointless assays and the costs to the health care system can be reduced both by enhancing and improving the educational standards of the requesting neurologists

The impact of an educational intervention, the New GP Contract and NICE guidelines on anti-epilepsy therapeutic drug monitoring

Background Since the early 1970s therapeutic drug monitoring (TDM) of anti-epilepsy drug (AED) levels has been available to assist in the review process of patients with epilepsy. Routine blood levels were not part of the Quality and Outcomes Framework in the New GP Contract, neither have they been generally recommended in National Guidelines (NICE and SIGN) for the management of patients with epilepsy. Aim To assess the impact of an educational intervention, the New GP Contract and NICE guidelines on the number of requests for TDM. Design Retrospective study. Setting 39 general practices serving Chester (13), the Rural area surrounding Chester (13) and Ellesmere Port (13). Methods An educational intervention took place in the individual Chester practices between December 2001 and March 2003. For the Rural and Ellesmere Port practices there was one combined event in March 2004 and in March 2007, respectively. Practices were encouraged, not to routinely request TDM, except in certain circumstances. The number of TDM requests for Chester, Rural and Ellesmere Port were obtained from the local laboratory in Chester, plus other nearby hospitals, to provide control groups. Main outcome measures The number of TDM requests from primary care for Chester, Rural, Ellesmere Port, Wirral, Crewe, Warrington and Wrexham, April to April, 2002 through to 2008, where available. Results There has been a fall in the number requests in all districts. The most significant falls were in Chester (47%), Rural (34%) and Ellesmere Port (47%), and corresponded to the time of their educational intervention. The fall has been less marked in Wirral (25%), Crewe (27%), Wrexham (10%) and Warrington (9%). In 2004, the first year after the introduction of the New GP Contract, TDM in Chester and the Rural fell significantly, while those in Ellesmere Port, Wirral, Crewe and Wrexham increased. TDM dropped significantly in Ellesmere Port in the year after their educational intervention. Despite the valproate assay being clinically unhelpful there were still 611 requests in the areas studied in 2007/2008. Conclusion The overall number of TDM requests has fallen since 2004 with the introduction of the New GP Contract and National Guidelines on the management of patients with epilepsy. The reduction has been more significant in areas where the changes were supplemented by an educational intervention. PCTs should endeavour to facilitate the introduction of National Guidelines with a supportive educational process, facilitated by educators with an interest and stake hold in those specific dillnesses. There is a significant cost to the NHS of inappropriate requests for TDM. Further study is required to quantify the indications for current requests for TDM.

Role of Therapeutic Drug Monitoring in HIV Therapy

Background: Therapeutic drug monitoring (TDM) is increasingly becoming part of the management of antiretroviral therapy for the treatment of HIV.Aim: To review the role of TDM in HIV therapy focusing on the indications for its use and resultant changes to drug therapy.Method: A 6‐month retrospective review of protease inhibitor TDM requests made by HIV clinicians was conducted. Patient medical records, STOCCA (dispensing program), pathology and the HIV outpatient unit database were reviewed to classify each TDM episode according to indication and outcome.Results: 50 protease inhibitor TDM requests were identified for 38 patients. Indications for use ofTDM included 47 cases of suspected inadequate dosing, two suspected toxicities and one suspected drug interaction. Therapy was altered in approximately 16% of all protease inhibitor TDM requests. Drug dose alterations were recorded for 7 of 4 7 levels measured for adequate dosing and 1 of the 2 levels measured for suspected toxicities.Conclusion: TDM is a valuable tool in managing antiretroviral therapy. It may play an important role in detecting both suboptimal or potentially toxic levels of protease inhibitors, which is an important factor in the success of antiretroviral therapy and the management of HIV.