Dose Adjustment In Renal Failure Research Articles

Post-transplant Diabetes Mellitus: What Physicians Need to Know.

Post-transplant diabetes mellitus (PTDM) is a common problem among solid organ transplant recipients contributing to morbidity and affecting patient as well as graft survival adversely. It can occur at any period following transplantation, but maximum incidence is observed in the first few months, with a second peak after a few years after transplantation. The pathogenesis is complex and poorly understood, however, it is associated with both dysfunctional beta-cells and insulin resistance. Both nonpharmacologic and antidiabetic therapies are important for adequate glycemic control. This point of view article provides a short review on PTDM in solid organ transplantation (SOT) recipients from a general physician's perspective.

Mobile Health Apps Providing Information on Drugs for Adult Emergency Care: Systematic Search on App Stores and Content Analysis.

BackgroundDrug-referencing apps are among the most frequently used by emergency health professionals. To date, no study has analyzed the quantity and quality of apps that provide information on emergency drugs.ObjectiveThis study aimed to identify apps designed to assist emergency professionals in managing drugs and to describe and analyze their characteristics.MethodsWe performed an observational, cross-sectional, descriptive study of apps that provide information on drugs for adult emergency care. The iOS and Android platforms were searched in February 2021. The apps were independently evaluated by 2 hospital clinical pharmacists. We analyzed developer affiliation, cost, updates, user ratings, and number of downloads. We also evaluated the main topic (emergency drugs or emergency medicine), the number of drugs described, the inclusion of bibliographic references, and the presence of the following drug information: commercial presentations, usual dosage, dose adjustment for renal failure, mechanism of action, therapeutic indications, contraindications, interactions with other medicinal products, use in pregnancy and breastfeeding, adverse reactions, method of preparation and administration, stability data, incompatibilities, identification of high-alert medications, positioning in treatment algorithms, information about medication reconciliation, and cost.ResultsOverall, 49 apps were identified. Of these 49 apps, 32 (65%) were found on both digital platforms; 11 (22%) were available only for Android, and 6 (12%) were available only for iOS. In total, 41% (20/49) of the apps required payment (ranging from €0.59 [US $0.64] to €179.99 [US $196.10]) and 22% (11/49) of the apps were developed by non–health care professionals. The mean weighted user rating was 4.023 of 5 (SD 0.71). Overall, 45% (22/49) of the apps focused on emergency drugs, and 55% (27/49) focused on emergency medicine. More than half (29/47, 62%) did not include bibliographic references or had not been updated for more than a year (29/49, 59%). The median number of drugs was 66 (range 4 to >5000). Contraindications (26/47, 55%) and adverse reactions (24/47, 51%) were found in only half of the apps. Less than half of the apps addressed dose adjustment for renal failure (15/47, 32%), interactions (10/47, 21%), and use during pregnancy and breastfeeding (15/47, 32%). Only 6% (3/47) identified high-alert medications, and 2% (1/47) included information about medication reconciliation. Health-related developer, main topic, and greater amount of drug information were not statistically associated with higher user ratings (P=.99, P=.09, and P=.31, respectively).ConclusionsWe provide a comprehensive review of apps with information on emergency drugs for adults. Information on authorship, drug characteristics, and bibliographic references is frequently scarce; therefore, we propose recommendations to consider when developing an app of these characteristics. Future efforts should be made to increase the regulation of drug-referencing apps and to conduct a more frequent and documented review of their clinical content.

Dose Adjustment in Renal Failure

Dose Adjustment in Renal Failure

The Role of Qutenza® (Topical Capsaicin 8%) in Treating Neuropathic Pain from Critical Ischemia in Patients with End-Stage Renal Disease: An Observational Cohort Study.

Current treatment strategies for painful critical ischemia in patients with end-stage renal disease (ESRD) are suboptimal. A drug that is non-renally excreted has minimal systemic absorption and does not require dose adjustment in renal failure is attractive. The aim of this study was to evaluate the safety and efficacy of Qutenza® (topical capsaicin 8%) for chronic neuropathic pain from critical ischemia in patients with ESRD. A prospective cohort study was conducted in a single-center, university teaching hospital. Twenty patients with ESRD were treated with Qutenza® for neuropathic pain from critical limb ischemia. Patients were followed-up at 1, 6 and 12 weeks post-treatment. The primary end point was the difference in visual analog scale (VAS) between baseline and week 12. Secondary end points were Brief Pain Inventory questionnaire (BPI) scores, quality of life assessment (EQ-5D) and patient global impression of change (PGIC). Safety and tolerability data were also collected. The trial was prospectively registered with clinical trials databases (EudraCT: 2012-001586-32; NCT01704313). There was significant reduction in VAS from baseline to week 12 (-20+/-7%; P = 0.02). There was a significant reduction in all seven domains of the BPI. Quality of life also improved at 12 weeks following treatment in two of the EQ-5D domains (mobility and pain). Qutenza® was well tolerated with no significant side effects in this patient cohort, which included 20% diabetics. In this small, observational study Qutenza® treatment has been shown to be effective and well-tolerated to treat neuropathic pain from critical ischemia in patients with ESRD.

Metformin associated lactic acidosis (MALA): clinical profiling and management.

Metformin (MF) accumulation during acute kidney injury is associated with high anion gap lactic acidosis type B (MF-associated lactic acidosis, MALA), a serious medical condition leading to high mortality. Despite dose adjustment for renal failure, diabetic patients with chronic kidney disease (CKD) stage III-IV are at risk for rapid decline in renal function by whatever reason, so that MF toxicity might arise if the drug is not timely withdrawn. Sixteen consecutive patients were admitted to our Hospital's Emergency Department with clinical findings consistent with MALA. Fifteen had prior history of CKD, 60% of them with GFR between 30 and 60ml/min. Of these, 5 required mechanical ventilation and cardiovascular support; 3 promptly recovered renal function after rehydration, whereas 10 (62%) required continuous veno-venous renal replacement treatment. SOFA and SAPS II scores were significantly related to the degree of lactic acidosis. In addition, lactate levels were relevant to therapeutic choices, since they were higher in dialyzed patients than in those on conservative treatment (11.92mmol/l vs 5.7mmol/l, p=0.03). The overall death rate has been 31%, with poorer prognosis for worse acidemia, as serum pH was significantly lower in non-survivors (pH 6.96 vs 7.16, p>0.04). Our own data and a review of the literature suggest that aged, hemodynamically frail patients, with several comorbidities and CKD, are at greater risk of MALA, despite MF dosage adjustment. Moreover, renal replacement therapy rather than simple acidosis correction by administration of alkali seems the treatment of choice, based on eventual renal recovery and overall outcome.

Evaluation of the appropriateness of imipenem/cilastatin prescription and dosing in a tertiary care hospital.

BackgroundImipenem/cilastatin is an antibacterial agent of the carbapenem class of β-lactams that is known to have an extremely wide spectrum of activity against Gram-positive, Gram-negative, aerobic, anaerobic, and even multidrug-resistant strains. The objective of this study was to evaluate the appropriate use of imipenem/cilastatin in a local tertiary care hospital. The study assessed the indication both empirically and after the culture results were available, the dose and dose adjustment in renal failure, as well as the incidence of seizure in hospitalized patients receiving imipenem/cilastatin.MethodsThis observational study was conducted in a tertiary care hospital over a 3-month period. The treatment of 100 patients with imipenem/cilastatin was evaluated both empirically and after culture results were available. Analysis of the appropriateness of imipenem/cilastatin indication, dose, and monitoring of seizure frequency was based on the package insert, updated published guidelines, and clinical judgment.ResultsPatients from internal medicine and intensive care units comprised approximately 50% of the population in the study. The patients received imipenem/cilastatin mainly for urinary tract infections (27%) or for sepsis of an unknown focus (22%). The use of imipenem/cilastatin empirically was appropriate in 97.2% (n=69/71) of the cases, and its use postculture in 86% of the cases. There were 29% of the patients who were not started on imipenem/cilastatin empirically. Four patients out of the 29 patients (13.8%) who were not started on imipenem/cilastatin empirically inappropriately received imipenem/cilastatin post-culture results. Thirty-three patients (33%) were not dosed appropriately, 30 of whom had renal impairment and creatinine clearance fluctuations. Only one patient developed a seizure while on imipenem/cilastatin.ConclusionThe prescription of imipenem/cilastatin at our setting was mostly appropriate to what is recommended in the guidelines and the literature, although a few cases could have been managed better. Dosage adjustment, however, was not as appropriate, mainly in patients who did not have a stable creatinine clearance.

DI-015 Antiretroviral modifications. Reasons for change

BackgroundGiven the high budgetary impact of antiretroviral therapy (ART) and the lack of adherence to sometimes complex HIV treatment, it is interesting to analyse the reasons for changes between different...

PS-007 A 24-month study of the interventions on electronic prescribing made by the Pharmacy Department

BackgroundOne of the activities of the pharmacist in a hospital is the screening of the electronic treatments for inpatients. During this process, some errors can be found in prescriptions. Pharmacist...

CP-019 Hospital pharmacists’ interventions in a central hospital

BackgroundSeveral studies have demonstrated the positive impact of clinical pharmacy services in the hospital setting. Interventions by clinical pharmacists have been shown to reduce the frequency of drug-related problems.Pharmacist interventions...

Kidney function and clinical recommendations of drug dose adjustment in geriatric patients.

BackgroundIn elderly patients chronic kidney disease often limits drug prescription. As several equations for quick assessment of kidney function by estimating glomerular filtration rate (eGFR) and several different clinical recommendations for drug dose adjustment in renal failure are published, choosing the correct approach for drug dosage is difficult for the practitioner. The aims of our study were to quantify the agreement between eGFR-equations grouped by creatinine-based or cystatin C-based and within the groups of creatinine and cystatin C-based equations and to investigate whether use of various literature and online references results in different recommendations for drug dose adjustment in renal disease in very elderly primary care patients.MethodsWe included 108 primary care patients aged 80 years and older from 11 family practices into a cross-sectional study. GFR was estimated using two serum creatinine-based equations (Cockroft-Gault, MDRD) and three serum cystatin C-based equations (Grubb, Hoek, Perkins). Concordance between different equations was quantified using intraclass correlation coefficients (ICCs). Essential changes in drug doses or discontinuation of medication were documented and compared in terms of estimated renal function as a consequence of the different eGFR-equations using five references commonly used in the US, Great Britain and Germany.ResultsIn general, creatinine-based equations resulted in lower eGFR-estimation and in higher necessity of drug dose adjustment than cystatin C-based equations. Concordance was high between creatinine-based equations alone (ICCs 0.87) and between cystatin C-based equations alone (ICCs 0.90 to 0.96), and moderate between creatinine-based equations and cystatin C-based equations (ICCs 0.54 to 0.76). When comparing the five different references consulted to identify necessary drug dose adjustments we found that the numbers of drugs that necessitate dose adjustment in the case of renal impairment differed considerably. The mean number of recommended changes in drug dosage ranged between 1.9 and 2.5 per patient depending on the chosen literature reference.ConclusionsOur data suggest that the choice of the literature source might have even greater impact on drug management than the choice of the equation used to estimate GFR alone. Efforts should be deployed to standardize methods for estimating kidney function in geriatric patients and literature recommendations on drug dose adjustment in renal failure.

GRP-021 Analysis of Pharmacist Interventions During the Validation of the Electronic Prescriptions in a Spanish Hospital

BackgroundComputerized provider-order-entry (CPOE) system is known to improve quality, increase efficiency, and reduce medication errors.The pharmacist, through the electronic validation, can provide improvements to the patient pharmacotherapy. However, not all...

PHC-009 Drug Dose Adjustment in Renal Failure

BackgroundIn renal failure, alteration in the pharmacokinetics increases the frequency of overdoses.Purpose To evaluate pharmaceutical care using a computer programme for drug dose adjustment in renal failure.Materials and Methods The...

Analysis of pharmaceutical interventions carried out via electronic prescriptions†

BackgroundHospital pharmacists play an important role in pharmacotherapy. Pharmaceutical care contributes to securing efficacy and safety in the use of medicines. Validation of the prescriptions allows pharmacists to detect, prevent...

In AL Amyloidosis, Both Oral Melphalan and Dexamethasone (Mel-Dex) and Risk-Adapted Cyclophosphamide, Thalidomide and Dexamethasone (CTD) Have Similar Efficacy as Upfront Treatment.

Abstract 745The treatment of AL amyloidosis has evolved rapidly over the last few years. The role of autologous stem cell transplantation is controversial and oral combination chemotherapy is often the treatment of first choice. The optimal induction regime is not uniformly agreed upon although some consider oral Mel-Dex as the current “standard of care”. We report our large experience with both Mel-Dex and CTD as upfront treatment for AL amyloidosis in a comparative retrospective study and compare these findings with those of our smaller prospective randomized trial (UKATT), also to be presented as this meeting, using the same treatment regimens (Gillmore et al).Patients treated with Mel-Dex and CTD as first-line treatment between 2002–2009 were identified from the database of the UK National Amyloidosis Centre, London. Organ involvement and responses were assessed according to international consensus criteria (Gertz et al, 2005).The results are summarised below. Our CTD experience has previously been reported at this Congress (Gibbs et al, 2008). A total of 58 patients received Mel-Dex and 122 patients received CTD as upfront therapy. The baseline characteristics of the two groups were not significantly different in terms of median number of organs involved (by both consensus criteria and 123I labelled serum amyloid P component (SAP) scintigraphy), cardiac involvement, creatinine clearances (CrCl) <30ml/min, and NT-ProBNP levels. The Mel-Dex group was an older population, and there was a trend that their CrCl was lower at diagnosis.The median number of cycles administered for both treatments was 5 (range 1–15). More patients presenting with neurological involvement were treated with Mel-Dex. The clonal response rates between the two regimens were not significantly different. The median time to best serum free light chain response (FLC) response for CTD was 2 months (range 1–5 months) versus 3 months for Mel-Dex (range 1–7). At 12 months, organ responses were observed in 44/113 (39%) patients treated with CTD compared to 12/56 (21%) patients treated with Mel-Dex (p = 0.03). Most Mel-Dex responses were renal.The median follow-up is 19 months and the median time to clonal progression was not reached in either group. There was no significant difference in the estimated overall survival at 3 years.Toxicity of any grade was reported by 76% of Mel-Dex patients and 84% of CTD patients (p=0.30). The commonest severe toxicity in both groups was fluid retention.In conclusion, this is the largest comparative series of oral Mel-Dex and CTD in AL amyloidosis. Both regimes are not significantly different in terms of complete (CR) and overall response (OR) rates, toxicity, time to clonal progression or overall survival. There is a suggestion that time to best FLC responses with Mel-Dex is slower than CTD (3 vs 2 months). These results concur with the results of our prospective UKATT trial. Mel-Dex has the disadvantages of being a stem cell toxic regimen, requiring dose adjustment in renal failure. CTD is a reasonable alternative to Mel-Dex in the treatment of AL amyloidosis and a large international randomized prospective trial should be considered.Patient Characteristics at DiagnosisMel-DexCTDp-valueNumber of patients58122Median age (years)7264<0.0001Males (%)7146Lambda FLC excess (%)7175Abnormal SAP scintigraphy (%)9185Median number organs involved22Median NT Pro-BNP (pmol/L)1241740.84Median Creatinine (umol/L)9392Median CrCl (ml/min)59730.07CrCl <30ml/min1415Organs Involved (% patients)Kidney8677Cardiac4748Nervous System3316Liver1018Gastrointestinal107Soft Tissue3119Treatment ResponsesFLC CR, n (%)14/45 (31%)36/96 (38%)FLC PR, n (%)20/45 (44%)40/96 (42%)Overall CR10/56 (18%)28/117 (24%)0.48Overall PR28/56 (50%)46/117 (39%)Overall Response38/56 (68%)74/117 (63%)0.67Organ responses12/56 (21%)44/113 (39%)0.03Renal organ responses11/50 (22%)35/96 (36%)0.11Median time to FLC PR (months)21Median time to best FLC response (months)32Toxicity, any grade44/58 (76%)102/122 (84%)0.30Overall survival at 3 years44/57 (77%)90/122 (74%)NS Disclosures:Off Label Use: Off-label use of thalidomide.

Managing anticoagulant related coagulopathy

There are several parenteral anticoagulants in use currently in the US. These include unfractionated heparin (UFH) commonly referred to as heparin, low-molecular weight heparins (LMWHs), synthetic pentasaccharide (fondaparinux), vitamin K antagonists (VKA) and direct thrombin inhibitors. The properties including mode of elimination, half-life, antidote and dose adjustment in renal failure of these drugs are listed in Table 1. VKA are the only orally approved anticoagulants with warfarin being the most commonly used in the United States with approximately three million users. This number of chronic warfarin users continues to increase annually as the baby boomers age and as patients over the age of 65 increase. It is estimated that approximately 26,000 major bleeding events occur annually in the United States. According to a recent study the incidence of anticoagulant associated intracerebral hemorrhage, the most feared and morbid bleeding complication, has quintupled in the US population in the 1990s [1]. The majority of this change can be explained by increasing warfarin use. A recent prospective study of 101 consecutive inpatients admitted to a tertiary care hospital in Boston [2] that looked at a cohort of patients with anticoagulation-associated hemorrhage suggested that excessive anticoagulation contributed independently to increased morbidity and mortality in hospitalized patients. The overall mortality at 60 days was 26% (13/50) in the excessive group compared with 10% (5/51) in the nonexcessive group (P = .03). Excessive warfarin therapy was associated with an increased 60-day mortality (P = .049), in contrast to excessive anticoagulation with UFH or LMWH alone (P = .27) or UFH or LMWH as a ‘‘bridge’’ to warfarin therapy (P = .10). Multivariate regression identified excessive anticoagulation as an independent predictor of 60-day mortality (adjusted hazard ratio [HR], 4.17; 95% confidence interval [CI], 1.39–12.49; P = .01), along with intracranial hemorrhage (adjusted HR, 6.16; 95% CI, 1.75– 21.67; P = .005) and active cancer (adjusted HR, 3.79; 95% CI, 1.13–12.70; P = .03).

Pharmacodynamic dose adjustment in renal failure: importance of the Hill coefficient

The most commonly applied pharmacodynamic model is the sigmoid E(max) model which can be applied for evaluation of dose adjustment schemes in renal failure. It is not known whether the Hill coefficient (H) is a shape factor that only improves the mathematical fit or whether the Hill coefficient is a pharmacodynamic parameter that independently affects drug effects and drug dosage adjustment. We performed simulations applying a mechanism-based mathematical pharmacokinetic-pharmacodynamic model for antimicrobial drugs. For the case of renal failure, two dose adjustment rules were evaluated. Administering the drug as 3 dose fractions per day increased the predicted total effect in the case of H = 1 but decreased the predicted total effect in the case of H = 2 compared to once-daily dosing. In renal failure, administration of the normal dose and prolongation of the interval leads to an increased total effect for the simulated drugs for both cases, namely H = 1 and H = 2. However, reducing the dose in renal failure might produce underdosage for a drug with a high Hill coefficient. The predicted effects of once- versus thrice-daily dose fractions as well as the predicted effects of dose reduction versus interval prolongation in renal failure critically depend on the Hill coefficient. Methods to estimate the Hill coefficient more precisely should be explored.

Impact of serum creatinine measurement error on dose adjustment in renal failure.

Doses of renally eliminated drugs should be adjusted according to kidney function to prevent adverse drug events and cost. Dose adjustment can be based on serum creatinine level, subsequent creatinine clearance estimation, and dosage calculation with consideration of the renal elimination properties of the respective compound. Our objective was to quantify the impact and relevance of serum creatinine measurement error on dose adjustment in renal failure. We analyzed 27914 measurements from external quality assessment surveys of 1878 German laboratories that used a kinetic alkaline picrate (69% of results) or an enzymatic method (25%) for creatinine determination. Linear models were fit for both methods combined and separately. On the basis of 95% confidence intervals (CIs) for creatinine values, 95% CIs for drug dosing were calculated. The 95% CI for a measured serum creatinine value was 0.80. Measured value < Reference method value < 1.28. Measured value for the kinetic alkaline picrate method and 0.87. Measured value < Reference method value < 1.21. Measured value for the enzymatic method. Applied to a data set of 6.5 million simulated patients with all possible combinations of characteristics relevant for drug dosing, the dosing error caused by serum creatinine measurement error did not exceed 25% in patients with creatinine clearance estimates lower than 50 mL/min according to the Cockcroft-Gault equation. For drugs completely eliminated by the kidneys in active form, the dosing error was up to 6-fold smaller than that which would occur if doses were not adjusted. The serum creatinine measurement error of current laboratory methods is small and is comparable to other errors influencing dose adjustment.

Renal handling of angiotensin receptor blockers: clinical relevance.

Angiotensin receptor blockers (ARBs), like angiotensin-converting enzyme (ACE) inhibitors, are commonly used in the setting of chronic kidney disease. The use of drugs in this class, or for that matter any drug in the renally compromised patient, should raise consideration of the impact of renal disease on the systemic elimination of the compound. Unlike most of the drugs in the ACE inhibitor class, the compounds making up the ARB class undergo significant hepatic elimination; thus, in the renal failure patient, they are not prone to relevant degrees of systemic accumulation with repetitive dosing. ARBs do not require dose adjustment in renal failure on the basis of their pharmacokinetic pattern; rather, dose reduction should be an empiric process dictated by having reached or exceeded the goal established for blood pressure reduction.

The arteriovenous fistula.

The ground-breaking article by Brescia and Cimino in 1966 ([1][1]) revolutionized the creation of the vascular access, and the Cimino fistula was soon used in almost all dialysis patients. Unfortunately, subsequent wide-spread use of PTFE grafts instead of AV fistulae occurred because of the ease of

Dose Adjustment in Renal Failure

Dose Adjustment in Renal Failure