Alterations in Drug Doses in Patients with Renal Failure



A considerable number of commonly used dru«s require alterations in the amount or timing of administration in patients with renal failure. In patients who are undergoing dialysis, the clinical problem is further compounded. Owing to differ­ences in the permeability of the membranes in­volved and the duration of the procedures, there are differences in the kinetics of drugs in patients undergoing hemodialysis as compared to those treated by peritoneal dialysis.

Drugs such as those listed on Table 35-2 require no alteration in dose in the patient with renal in­sufficiency. The metabolism of these drugs is pre­dominantly by nonrenal routes and is not signif­icantly altered by the presence of renal failure or the “uremic” environment. Table 35-3 lists drugs that should not be administered to patients with renal failure. Table 35-4 provides a partial listing of clinically important drugs whose metabolism is significantly altered in the patient with renal disease. For drugs that are eliminated from the body exclusively by renal excretion, the adjust­ment in dosing correlates with the degree of renal impairment. For drugs that are only partially ex­creted by the kidney, other formulas and nomo­grams are used.

In general, two methods are used to adjust drug regimens in patients with renal disease who are receiving drugs whose metabolism is altered. Either the amount of drug administered is reduced but the dosing interval is held constant or the amount of drug administered per dose is held con­stant but the dosing interval is lengthened. The choice between these two methods depends upon the characteristics of the drug in question and the clinical effect desired. For the drugs in common usage, drug-dosing nomograms for use in patients with renal failure have been published and these nomograms provide a useful tool in the ordering of drugs. It is important to note, however, that the changes in drug metabolism in the patient with renal failure are complex and that exclusive re­liance on a nomogram alone is fraught with con­siderable danger. Careful clinical and laboratory assessment of the patient is required. If available, blood levels of the drug or drugs should be ob­tained. The above points can be illustrated by con­sidering the administration of an aminoglycoside antibiotic to a patient with sepsis and renal dys­function. Use of any of the published drug-dosing nomograms for a specific aminoglycoside anti­biotic is associated with a significant number of patients who achieve blood levels of drug below that required to achieve a therapeutic effect. There is also a significant number of patients whose blood concentrations of drug are in the “toxic” range. This may be associated with the develop­ment of overt toxicity. In the case of the amino­glycosides, toxicity may be manifest by further de­terioration in renal function. While therapeutic blood levels of drugs do not necessarily insure that drug-related toxicities will not occur, when used in conjunction with clinical assessment of the patient, the possibility of drug-related disease may be minimized.