Heather Nyman

Comparative evaluation of the Cockcroft-Gault Equation and the Modification of Diet in Renal Disease (MDRD) study equation for drug dosing: an opinion of the Nephrology Practice and Research Network of the American College of Clinical Pharmacy.

Accurate assessment of kidney function is an important component of determining appropriate drug dosing regimens. Nearly all manufacturer‐recommended dosage adjustments are based on creatinine clearance ranges derived from clinical pharmacokinetic studies performed during the drug development process. The Cockcroft‐Gault (CG) equation provides an estimate of creatinine clearance and is the equation most commonly used to determine drug dosages in patients with impaired kidney function. The Modification of Diet in Renal Disease (MDRD) study equation has also been proposed for this purpose. Published studies report that drug dosages determined by the two equations do not agree in 1 0–40% of cases. However, interpretation and comparison of these studies are complicated by the variable creatinine methods used for calculating CG and MDRD estimates, the patient populations studied, and a lack of outcomes data demonstrating the clinical significance of dosing discrepancies. Moreover, the impact of reporting standardized serum creatinine values on the accuracy of the CG equation and corresponding drug dosing regimens have been questioned. Currently, no prospective pharmacokinetic studies have been conducted with use of the MDRD equation to generate dosing recommendations, and limited data are available to support its use in some patient populations representing demographic extremes. Collectively, these issues have resulted in considerable confusion among clinicians and have fueled a healthy debate on whether or not to use the MDRD equation to determine drug dosages. Each of these issues is reviewed, and a proposed algorithm for using creatinine‐based kidney function assessments in drug dosing is provided. Knowledge of the advantages, limitations, and clinical role of each equation will facilitate their safe and effective use in drug dosing.

Use of estimated glomerular filtration rate for drug dosing in the chronic kidney disease patient

Purpose of reviewAssessment of kidney function is necessary to stage chronic kidney disease (CKD) and appropriately dose medications. The Cockcroft–Gault equation provides an estimate of creatinine clearance (eClCr) and is the method commonly referenced in pharmacokinetic studies. The Modification of Diet in Renal Disease (MDRD) and CKD-Epidemiology Collaboration (EPI) equations provide an estimate of glomerular filtration rate (eGFR), with the MDRD eGFR now automatically reported by most clinical laboratories. This review describes the differences in the Cockcroft–Gault, MDRD, and CKD-EPI equations and considerations when applying estimates from these equations for drug dosing. Recent findingsStudies evaluating drug-dosing regimens using eClCr and eGFR differ in their results depending on the population in which the equation is applied, the adjustment factors used to account for body size, and the number of dosing levels for a particular medication. The largest study to evaluate drug regimen design by method concluded that either the eGFR or Cockcroft–Gault estimates could be used for drug dosing. Differences in methodology among studies are a key factor in evaluating these results and will be highlighted in this review. SummaryThe Cockcroft–Gault, MDRD, and CKD-EPI equations provide reasonable estimates of kidney function; however, clinicians must understand the limitations when using these estimates for drug regimen design.

Workplace Contamination with Antineoplastic Agents in a New Cancer Hospital Using a Closed-System Drug Transfer Device

Objective To determine levels of environmental chemotherapy contamination in a new cancer hospital that has exclusively used a closed-system drug transfer device (PhaSeal) for preparing and administering all compatible antineoplastics. Methods After 6 months of operation, surface samples were collected from pharmacy and nursing areas to determine levels of contamination with cyclophosphamide and ifosfamide. In addition, urine samples were collected from pharmacists, pharmacy technicians, and nurses to determine employee exposure to these agents. All samples were analyzed using liquid chromatography/tandem mass spectrometry. Results Twenty-one percent (7/34) of surface samples collected tested positive for cyclophosphamide contamination. Twelve percent (4/34) of surface samples tested positive for ifosfamide. To place this into perspective, historical data collected at our outpatient oncology infusion clinic 6 months after converting to PhaSeal from conventional methods of antineoplastic preparation showed 33% (7/21) and 71% (15/21) of samples tested positive for cyclophosphamide and ifosfamide, respectively. The level of ifosfamide contamination found in samples that tested positive at our new hospital also appeared to be lower than in positive samples at the outpatient infusion clinic. In the current study, the urine of one participant (1/11), a pharmacy technician, tested positive for low levels of cyclophosphamide and ifosfamide. To compare, 71% and 0% of participants tested at the outpatient infusion clinic had positive urine samples prior to and 6 months after implementation of PhaSeal, respectively. Conclusions: Compared with historical levels of contamination in our outpatient oncology infusion clinic, levels of chemotherapy contamination appeared lower. However, some contamination was still present in our new cancer hospital where PhaSeal had been used exclusively.

Health Care Costs in a Cohort of HIV-Infected U.S. Veterans Receiving Regimens Containing Tenofovir Disoproxil Fumarate/Emtricitabine

BACKGROUNDnTenofovir disoproxil fumarate (TDF), a key component in many human immunodeficiency virus (HIV) treatment regimens, is associated with increased renal and bone toxicities. The contributions of such toxicities to treatment costs, as well as the relative differences in treatment costs for various TDF/emtricitabine (FTC) regimens, remains unexplored.nnnOBJECTIVEnTo estimate and compare mean overall and renal- and bone-specific costs, including total, inpatient, outpatient, and pharmacy costs in patients treated with TDF/FTC+efavirenz (EFV) compared with several non-EFV-containing TDF/FTC regimens.nnnMETHODSnWe conducted a national cohort study of treatment-naive HIV-infected U.S. veterans who initiated treatment from 2003 to 2015 with TDF/FTC in combination with EFV, elvitegravir/cobicistat, rilpivirine, or ritonavir-boosted protease inhibitors (atazanavir, darunavir, or lopinavir). Outcomes of interest were quarterly total, inpatient, outpatient, and pharmacy costs using data from the Veterans Health Administration (VHA) electronic medical record and Managerial Cost Accounting System (an activity-based accounting system that allocates VHA expenditures to patient encounters). We controlled for measured confounders using inverse probability of treatment (IPT) weights and assessed differences using standardized mean differences (SMDs). For comparisons where SMDs exceeded 0.1 after IPT weighting, we used the more conservative matching weights in sensitivity analyses. For hypothesis testing, we compared IPT-adjusted differences in quarterly costs between treatment groups using Mann-Whitney U-tests and generalized estimating equation (GEE) regression models.nnnRESULTSnOf 33,048 HIV-positive veterans, 7,222 met eligibility criteria, including 4,172 TDF/FTC + EFV recipients; mean (SD) age of the cohort was 50.0 (10.0) years; 96.7% were male; 60.1% were black; and 30.1% were white. Quarterly periods of exposure to EFV-containing regimens were 22,499 and of exposure to non-EFV-containing regimens were 11,633. After IPT weighting, absolute SMDs were < 0.1 except for a few covariates in the rilpivirine comparison. The per-patient adjusted mean total quarterly costs were

Tenofovir-Associated Bone Adverse Outcomes among a US National Historical Cohort of HIV-Infected Veterans: Risk Modification by Concomitant Antiretrovirals

7,145 for EFV versus

Removal of vancomycin administered during dialysis by a high-flux dialyzer: Vancomycin removal in dialysis

8,726 for non-EFV (P < 0.001; Mann-Whitney U-test) and the per-patient adjusted mean difference in total quarterly costs was

Renal dosing in high-risk populations.

1,419 lower for EFV versus all non-EFV combined (P < 0.001; GEE model). Corresponding values for outpatient costs (

Assessing and treating hepatic encephalopathy in the older patient.

2,656 vs.

Tenofovir-Associated Nephrotoxicity Among a US National Historical Cohort of HIV-Infected Veterans: Risk Modification by Concomitant Antiretrovirals

2,942; P < 0.001; difference, -

Renal and Bone Outcomes Among HIV-Infected Patients Exposed to EFV/TDF/FTC Compared With Other Tenofovir Disoproxil Fumarate–Containing Antiretroviral Regimens: Findings From the Veterans Health Administration (VHA)

254; P = 0.001), inpatient costs (