Dosing regimens renal impairment

The Food and Drug Administration (FDA) approved dose of daclizumab is 1 mg/kg within 24 hours of transplant surgery and then 1 mg/kg administered every 2 weeks after surgery for a total of five doses.7,9,11 No dose adjustment is necessary in renal impairment, but no data are available for dose adjustments in hepatic dysfunction. Several trials have shown that a shorter dosing regimen of daclizumab, two doses given in a similar manner as basiliximab, may be as safe and effective as the full five-dose course.12,13... 

Upon the administration of 0.27 mg of a therapeutic agent to a normal individual, the elimination rate constant was found to be 0.0315 hour 1. The normal dosing regimen included 0.27 mg qid. If the elimination rate constant in renally impaired condition is 80% of the normal elimination rate constant, how can the dose be adjusted maintaining the same dosing interval of six hours ... 

Renal function impairment W th renal impairment, relative overdose might occur even with a standard dosage regimen. 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. Reduce the bolus dose and rate of infusion in patients with known or suspected renal insufficiency (see Administration and Dosage). 

Renal impairment Data in pediatric patients with impaired renal function are not available however, because cefepime pharmacokinetics are similar in adult and pediatric patients, changes in dosing regimen similar to those in adults are recommended for pediatric patients. 

Uncomplicated UTIs and gonorrhea - S ng e 400 mg dose regimen (for the treatment of uncomplicated UTIs and gonorrhea) and 200 mg once daily for 3 days regimen (for the treatment of uncomplicated UTIs) require no dosage adjustment in patients with impaired renal function. 

None of the tested covariates was identified as having a clinically relevant impact on the PK of cetuximab. Thus, changes in dose or dosing regimen do not appear to be necessary in any of the subpopulations defined by these covariates. However, it should be noted that the majority of the studied patients had adequate hepatic and renal function. Overall, more than 90 % of the patients included in the PK database had normal hepatic function, more than 60% had normal renal function, and a further 32% had only mild impairment (creatinine clearance 50-80 mL/min). Hence, the effect of more severe renal or hepatic impairment on cetuximab PK remains to be elucidated. 

In summary, the primary goal of a study in individuals with impaired renal function is to determine if the pharmacokinetic is altered to such an extent that the dose and/or dosing regimen of a drug should be adjusted from that established in the confirmatory safety and efficacy trials. 

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). 

Although differences in the incidence of renal adverse events between bisphosphonates have been reported from clinical trials, the reasons for these observations remain unknown but may be specific to a particular drug, dosing regimen, or prunary tumour type. Although more common in patients with pre-existing renal impairment, nephrotoxicity is not exclusive to this patient population. Clearly, further comparative chnical trials would be needed to directly compare the renal safety profiles of different i.v. bisphosphonates. 

This regimen would yield similar peak and trough concentrations in the renally impaired patient as in the patient with normal renal function, but there is a risk of missed doses with such an unorthodox interval (see Fig. 48-1, Scenario C). In addition, the prolonged period below the C s average concentration may be less than optimal. 

The recommended dosing regimen of topotecan is a 30-minnte infusion of 1.5 mg/m per day for 5 consecntive days every 3 weeks. As a significant fraction of the topotecan administered is excreted in the nrine, severe toxicities have been observed in patients with decreased creatinine clearance. Therefore, the dose of topotecan should be reduced to 0.75 mg/m per day in patients with moderate renal dysfunction (creatinine clearance 20 to 40 mL/minute), and topotecan shonld not be administered to patients with severe renal impairment (aeatinine clearance <20 mL/minute). Topotecan clearance and toxicity are not significantly altered in patients with hepatic dysfnnction, and therefore no dose reduction is necessary in these patients. 

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