Creatinine clearance dosing adjustments

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. 

Obtain a baseline serum creatinine measurement. Calculate the estimated creatinine clearance and adjust the dose of H2RAs and sucralfate according to package insert recommendations. 

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. ... 

The practical application of the use of creatinine clearance for adjusting the dose or dosage regimen of a dmg, which is being eliminated by kidneys, is illustrated in Tables 4.3 and 4.4. 

Carboplatin displays less nephro-, oto- and neurotoxicity. However, myelosuppression is more frequent, and as the drug is exclusively cleared through the kidney, adjustment of dose for creatinine clearance must be accomplished. 

Before administering this drug to an elderly patient or one that has renal impairment, the primary health care provider may order a creatinine clearance. The initial dose is 50 to 100 mg PO or IV, depending on the results of the creatinine clearance. The nurse reports the laboratory results to the primary health care provider because dosage adjustments may be made on the results of the creatinine clearance. 

Low molecular weight heparins (adjust dose for renal dysfunction [i.e., creatinine clearance <30 mL/min])... 

The dose of lamivudine is 100 mg orally once daily for treatment of chronic hepatitis B. The dose must be adjusted in patients with renal dysfunction [creatinine clearance (CrCl) less than 50 mL/minute]. 

The initial dose of allopurinol is based on the patient s renal function. Patients with creatinine clearances of 50 mL/minute or less should receive a starting dose of less than 300 mg/day to minimize adverse effects. The relationship between dose of allopurinol and its most severe side effects is controversial. However, the dose can be adjusted upward as needed and tolerated. It is reasonable to reduce the dose temporarily in patients who develop reversible acute renal failure. 

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

Voriconazole 6 mg/kg IV loading dose every 12 hours on day 1 followed by 4 mg/kg PO/IV every 12 hours Dosage adjustment in hepatic dysfunction IV formulation contraindicated if creatinine clearance less than 50 mDminute multiple drug interactions. 

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. 

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. 

Dosage in renal impairment Dosage adjustment isbased on creatinine clearance. Total digitalizing dose decrease by 50% in end-stage renal disease. 

Geriatric Considerations-Summary Adjust dose based on creatinine clearance. Not effective in preventing NSAID-induced gastric ulceration and bleeding proton pump inhibitors should be used for this indication instead. 

Heparin-induced thrombocytopenia and associated thromboembolic disease to prevent further thromboembolic complications IV, IV Infusion 0.2-0.4 mg/kg, IV slowly over 15-20 sec, followed by IV infusion of 0.1-0.15 mg/kg/hr for 2-10 days or longer. Dosaye in renal impairment Initial dose is decreased to 0.2 mg/kg, with infusion rate adjusted based on creatinine clearance. 

Geriatric Considerations - Summary Older adults are at high risk for EPS and TD. Adjust dose based on creatinine clearance. Long-term use (>3 mo) is not recommended. Adverse effects can occur at anytime during therapy. 

Creatinine Clearance Adjusted Dose Dosage Interval... 

Geriatric Considerations - Summary Well-tolerated in older adults. Adjust dose based on creatinine clearance. Autoinduction of metabolism does not occur as seen with carbamazepine, but drug interactions are still an issue. Many of the CNS effects occur early in treatment and are transitory. One-third of patients with hypersensitivity reactions to carbamazepine will experience cross-sensitivity to oxcarbazepine. 

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. 

Penicillin is rapidly excreted by the kidneys small amounts are excreted by other routes. About 10% of renal excretion is by glomerular filtration and 90% by tubular secretion. The normal half-life of penicillin G is approximately 30 minutes in renal failure, it may be as long as 10 hours. Ampicillin and the extended-spectrum penicillins are secreted more slowly than penicillin G and have half-lives of 1 hour. For penicillins that are cleared by the kidney, the dose must be adjusted according to renal function, with approximately one fourth to one third the normal dose being administered if creatinine clearance is 10 mL/min or less (Table 43-1). 

Antibiotic (Route of Administration) Adult Dose Pediatric Dose1 Neonatal Dose2 Adjusted Dose as a Percentage of Normal Dose for Renal Failure Based on Creatinine Clearance (Clcr) ... 

Intravenous cidofovir is effective for the treatment of CMV retinitis and is used experimentally to treat adenovirus infections. Intravenous cidofovir must be administered with high-dose probenecid (2 g at 3 hours before the infusion and 1 g at 2 and 8 hours after), which blocks active tubular secretion and decreases nephrotoxicity. Cidofovir dosage must be adjusted for alterations in the calculated creatinine clearance or for the presence of urine protein before each infusion, and aggressive adjunctive hydration is required. Initiation of cidofovir therapy is contraindicated in patients with existing renal insufficiency. Direct intravitreal administration of cidofovir is not recommended because of ocular toxicity. 

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

Measurements such as creatinine clearance have been used successfully to adjust dosing regimens for drugs eliminated primarily by the kidneys. Measures of hepatic function have been sought using endogenous... 

Hepatic and renal function. Patients with advanced cancer may have impaired liver function due to the presence of liver metastases. In this case drug doses may need to be adjusted. In the case of the FOLFOX regimen, 5-fluorouracil dose may need to be reduced if the impairment is moderate or severe. Mrs KT s baseline liver function tests indicate a normal liver function, but these parameters should be monitored carefully throughout treatment. Reduced renal function may also necessitate a decrease in drug dosage. In the case of the FOLFOX regimen, oxaliplatin is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min). 

BLEOMYCIN ANTICANCER AND IMMUNOMODULATING DRUGS-CISPLATIN t bleomycin levels, with risk of pulmonary toxicity Elimination of bleomycin is delayed by cisplatin due to 1 glomerular filtration. This is most likely with accumulated doses of cisplatin in excess of 300 mg/m2 Monitor renal function and adjust dose of bleomycin as per creatinine clearance. Monitor clinically, radiologically and with lung function tests for pulmonaiy toxicity... 

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