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Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function
1Department of Pharmacy Practice, University of Arizona Health Sciences Center, Tucson 85724.
Abstract:
The narrow therapeutic index of anticancer drugs presents a clinical dilemma when these agents are administered to patients with impaired or unstable renal function. The purpose of this review is to (i) describe the nephrotoxicity of certain anticancer drugs, (ii) evaluate the fraction of renal clearance for pertinent anticancer drugs, and (iii) make general recommendations for the dosing of these drugs in the presence of impaired renal function. Pharmacokinetic, pharmacodynamic, and clinical toxicity information was obtained from current scientific and clinical literature. Recommendations for dosage adjustment of drugs is based on their nephrotoxicity, or renal clearance equal to or exceeding 30% of the administered dose. The specific formula used to calculate dosage adjustment of renally cleared anticancer drugs is based on fundamental pharmacokinetic principles. In addition, prospectively validated formulae for the dosage adjustment of specific agents, such as carboplatin are also reviewed. Forty-eight anticancer drugs are reviewed in this report. Nephrotoxicity is associated with 12 of these agents (Table 1). Renal clearance equal to or exceeding 30% of the administered dose is a characteristic of 17 of the drugs studied (Table 2), and a general recommendation for dose adjustment of these anticancer drugs is presented in Table 3. Renal clearance that is less than 30% of the administered dose is a feature of 31 anticancer drugs (Table 4) included in this review. This report provides general guidelines to adjust doses of renally excreted or nephrotoxic anticancer drugs in patients who present with altered renal function.
Insights
This review details anticancer drug nephrotoxicity and renal clearance, offering dosing adjustment guidelines for patients with impaired kidney function. It aids clinicians in safely managing chemotherapy in renal dysfunction.
Area of Science:
- Pharmacology
- Nephrology
- Oncology
Background:
- Anticancer drugs pose risks for patients with kidney dysfunction due to narrow therapeutic indices.
- Managing chemotherapy in patients with impaired renal function requires careful consideration of drug toxicity and clearance.
Purpose of the Study:
- To review the nephrotoxicity of specific anticancer agents.
- To evaluate the renal clearance fraction for relevant anticancer drugs.
- To provide dosing recommendations for anticancer drugs in patients with renal impairment.
Main Methods:
- Literature review of pharmacokinetic, pharmacodynamic, and clinical toxicity data.
- Analysis of anticancer drugs based on nephrotoxicity and renal clearance (>30% or <30%).
- Application of pharmacokinetic principles for dosage adjustment formulas.
Main Results:
- Twelve of 48 reviewed anticancer drugs are associated with nephrotoxicity.
- Seventeen drugs exhibit renal clearance >= 30% of the administered dose.
- Thirty-one drugs have renal clearance < 30% of the administered dose.
Conclusions:
- General guidelines are presented for adjusting doses of renally excreted or nephrotoxic anticancer drugs.
- Dosing adjustments are crucial for optimizing safety and efficacy in patients with altered renal function.
- The review provides a framework for evidence-based chemotherapy dosing in renal impairment.