Creatinine dosing adjustments

The serum creatinine is measured to identify patients who may need dosing adjustments for some medications, as well as those who are at high risk of morbidity and mortality. 

Dosing adjustment based on Calvert equation Proportional to lower creatinine clearance, where normal equal to 70 mL/minute (0.67 mL/s x m2)... 

Drug therapy individualization for patients with renal insufficiency sometimes requires only a simple proportional dose adjustment based on creatinine clearance (CLcr). Alternatively, complex adjustments are required for drugs that are extensively metabolized or undergo dramatic changes in protein binding and distribution volume. 

Urine Urine is the principal route by which nonlactating humans excrete perchlorate [261, 262]. Urinary perchlorate provides a reasonable measure of human exposure because 70-95% of perchlorate dose is excreted unchanged in the urine with a half-life of 8 h [261-263]. Creatinine (CR) adjustment is typically used to minimize the effects of variation of analyte concentration in urine either among samples produced by different individuals or among samples produced by the same individual. 

The systemic clearance of lepirudin is proportional to the glomerular filtration rate or creatinine clearance. Dose adjustment based on creatinine clearance is recommended (see Administration and Dosage). In patients with marked renal insufficiency (creatinine clearance less than 15 mL/min) and on hemodialysis, elimination half-lives are prolonged 2 days or less. 

Renal impairment, the major toxicity, occurs to some degree in most patients. Continual assessment of a patient s risk and frequent monitoring of serum creatinine with dose adjustment for changes in renal function are imperative. 

Aduits with impaired renai function - A dose adjustment should not be necessary for patients with creatinine clearance (Ccr) greater than or equal to 15 mL/min. 

Creatinine Clearance Adjusted Dose Dosage Interval... 

Pharmacokinetics Lepirudin is eliminated primarily by renal excretion (renal clearance 65 to 115ml/min). Dose adjustment based on creatinine clearance is recommended. The total clearance of lepirudin is 195ml/min, its elimination half-life is 1.3 hours, and its volume of distribution is 12.2 to 18.0 hters.The systemic clearance of lepirudin in women is about 25% lower than in men. In elderly patients the systemic clearance of lepirudin is 20% lower than in younger patients. Distribution is limited to extracellular space. As the intravenous dose is increased over the range of 0.1 to 0.4mg/kg, the maximum plasma concentration and the area-under-the-curve increase proportionally. 

Pharmacokinetics According to the product label, the pharmacokinetics of eptihbatide are linear and dose proportional. Plasma elimination half-life is approximately 2.5 hours. The extent of eptihbatide binding to human plasma protein is about 25% its mean volume of distribution is 185mPkg. Clearance in patients with coronary artery disease is 55-58 ml/kg per hour. Clinical studies have included 2418 patients with serum creatinine between 1.0 and 2.0mg/dl without dose adjustment. No data are available in patients with more severe degrees of renal impairment, but plasma eptihbatide levels are expected to be higher in such patients. Patients in clinical studies were older than the subjects in clinical pharmacology studies, and they had lower total body eptihbatide clearance and higher eptihbatide plasma levels. Men and women showed no important differences in the pharmacokinetics of eptihbatide. 

Dosing Adjustments for Patients with Penal Impairment Creatinine % of Dosing... 

Dosing Adjustments for Patients with Renal Dysfunction Creatinine Clearance (mL/min) Dosina Regimen... 

In-hospital procedural success was achieved in 95% of patients. At 30 days, the incidence of the composite of death/MI/unplanned revascularization/amputation was 1.2%. In-hospital major bleeding occurred in 2.2% of the patients. In this study however, patients with a serum creatinine >4 mg/dl were excluded. No dose adjustment was made for renal insufficiency. There was no correlation between clinical outcome and the degree of renal impairment. 

From the standpoint of clinical pharmacology/ the utility of using the Cockcroft and Gault equation/ or other methods/ to estimate creatinine clearance stems from the fact that these estimates can alert healthcare workers to the presence of impaired renal function in patients whose creatinine formation rate is reduced. As discussed in Chapter 5, creatinine clearance estimates also can be used to guide dose adjustment in these patients. 

In patients with normal renal function, 70 to 90% of an intravenous dose of vancomycin is excreted in the urine unchanged by glomerular filtration. The serum elimination half-life in patients with normal renal function is variable, but averages 6 hours [171]. However, terminal half-lives ranging from 3 to 11 hours have been observed [184]. In anuric patients, the serum half-life increases markedly to 6 to 10 days [171]. The liver may also be involved in the disposition of vancomycin as dose adjustments have been required in patients with severe liver dysfunction [172]. An interesting study by Golper et al that compared systemic vancomycin clearance simultaneously with the renal clearances of vancomycin, creatinine, inulin and para-aminohippurate demonstrated a substantial non-renal clearance of vancomycin of 30%. In addition, the researchers found that the non-renal clearance of vancomycin was concentration dependent with a 10% greater clearance at serum concentrations of 14 mg/ ml as compared to 7 mg/ ml [185]. 

When estimating creatinine clearance in the elderly using the Cockcroft and Gault equation, some clinicians choose to round the value up to 1 if the patient s serum creatinine concentration is less than 1. Rounding the serum creatinine concentration may provide an underestimation of creatinine clearance and result in improper dose adjustment of renally eliminated medications. It is important to realize that the equation is merely an estimate, and attempts should be made to determine creatinine clearance accurately with certain medications (e.g., metformin). 

Because LMWHs are eliminated renally and patients with renal insufficiency generally have been exclnded from clinical trials, some practice protocols recommend UFH for patients with creatinine clearance rates of less than 30 mL/min. (Creatinine clearance is calculated based on total patient body weight.) However, recent recommendations for dosing adjnstment of enoxaparin in patients with creatinine clearances between 10 and 30 mL/min are now listed in the product manufacturer s label (see Table 16 ). Administration of LMWHs should be avoided in dialysis patients. UFH is monitored and the dose adjusted to a target aPTT, whereas LMWHs are administered by a fixed, weight-based dose. Other dosing information and contraindications are described in Table 16. ... 

Over 80% of foscamet is excreted unchanged in the urine. Plasma clearance is proportional to creatinine clearance, and dose adjustments are indicated for small decreases in renal function. Plasma elimination is complex, with an initial t of 4-8 hours and a prolonged terminal t of 4 days. Sequestration in bone with gradual release accounts for a 10—20% of a given dose. Foscamet is cleared efficiently by hemodialysis (-50% of a dose). 

The oral bioavailabihty of lamivudine is >80% and is not affected by food. It is excreted primarily unchanged in the urine, and dose adjustment is recommended for patients with a creatinine clearance of <50 mL/min. Lamivudine is one of the least toxic antiretrovirals and has few significant effects. Neutropenia, headache, and nausea have been reported. 

Daptomycin is a fermentation product having a cyclic lipopeptide structure. It is primarily active against Gram-positive infections, especially those involved in skin/skin structure infections. It is given IV but must be administered over a period of 30 minutes or more. It binds to cell membranes and causes depolarization, which interrupts protein, DNA, and RNA synthesis. Daptomycin is bactericidal. Although resistance can be achieved in vitro, resistance has been slow to emerge in the clinic. Patients should be monitored for muscle pain or weakness, because some incidence of elevated serum creatinine phosphokinase is associated with its use. A small number of clinical trial patients also developed conditions related to decreases in nerve conduction (e.g., paresthesias and Bell s palsy). Daptomycin is eliminated primarily by the kidney, so dose adjustment may be necessary in cases of renal insufficiency. 

Dosing Adjustment from the Use of Creatinine Serum Levels... 

An alternative method is the prospective approach, which uses patient information, such as serum creatinine, patient s age, weight, height, or body surface area to empirically estimate V, K, and creatinine clearance (Cl ). Adjustments to a maintenance dose are achieved through various approaches. The most significant application of either the retrospective or prospective approach is with regard to dosing adjustment in renal failure. ... 

If creatinine clearance is reduced, dose adjustment for dmgs that are eliminated by the kidneys must be considered. Failure to adjust the dose of a dmg will result in much higher blood... 

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