Drug Dosing in Patients with Renal Impairment
SAN DIEGO—Caution and collaboration are key to correctly dosing medications in patients with renal impairment, according to presenters in a session devoted to the topic at the Society for Critical Care Medicine 2011 annual meeting,
Session chair William Dager, PharmD, Clinical Professor of Pharmacy at the University of California Davis Medical Center, noted that physicians must rely on interdisciplinary collaboration to compensate for the lack of consensus in the literature about appropriate renal adjustment for many medications.
“The paradox here is that the nephrologist may not be completely aware of the intricacies of the pharmacology, and the pharmacologist or clinical pharmacist may not be aware of what's going on with the kidney and the dialysis setup,” Dr. Dager said. “So collaboration between the two, along with input from the primary care team, would be preferred in developing the optimal management regimen in many cases.”
A comparison of four different studies on dose adjustment in renal impairment showed that they differed in their recommendations for adjusting dosage and dosing interval and also in their definitions of renal impairment (BMJ 2005;331:263). In addition, the researchers did not cite any systematic reviews or cohort studies to support their recommendations.
The lack of a drug-dosing consensus is particularly acute among patients in the intensive care unit (ICU) on dialysis because very few studies have been performed in this population, Dr. Dager said.
One clinical situation in which there is a paucity of data is that of ICU patients with acute renal failure on extended-duration dialysis. These patients have reduced drug-concentration rebound compared with other dialysis patients.
Dynamic critically ill individuals with renal failure are another challenge. Absorption, distribution, metabolism, and elimination of medications vary in these individuals and they also may have other unusual challenging characteristics such as altered platelet function (Clin Infect Dis. 2006;42:1764-1771).
“One of the main problems is that the literature has not kept up with advancing dialysis technology,” Dr. Dager observed. “As nephrologists get more creative with the dialysis tools they have, they also have to remember that the pharmacology and dosing regimen also may need to be creatively adapted to each patient's parameters.”
Ty Kiser, PharmD, Assistant Professor of Clinical Pharmacy at the University of Colorado in Denver, noted that numerous patient characteristics affect drug clearance—including whether patients are children or adults and whether they have acute kidney injury or end-stage renal disease. Clinicians also must take into account machine-related factors, such as the dialysis mode, blood-flow rate, and treatment duration.
Drug characteristics also must be considered. With medications that have a wide therapeutic index and a low toxicity, the focus should be on being as “aggressive as possible, and as safe as necessary,” Dr. Kiser said. In contrast, drugs with a narrow therapeutic index or a high concentration-dependent toxicity should be dosed in a manner that is as “safe as possible, and as aggressive as necessary.”
He agrees that collaboration between pharmacists and nephrologists is critical. “If you put those two minds together you get the best outcome for your patient,” he said.
Another presenter, Marilee Obritsch, PharmD, provided an overview of the pharmacotherapeutic considerations in dosing some commonly used medications in renally compromised individuals. These include dabigatran (Pradaxa, Boehringer Ingelheim)—which should be delivered in a reduced dose of 75 mg twice daily in patients with a creatinine clearance of 15-30 mL/min—and eptifibatide—the infusion of which should be reduced to 1 mcg/kg/min if the creatinine clearance is below 50 mL/min.
Dr. Obritsch, who practices in the Southeast Alaska Regional Health Consortium in Juneau, advocates a six-step approach. These involves first estimating kidney function using standard equations, evaluating patients thoroughly, assessing the medications, weighing the risks and benefits of dose adjustment, documenting any adjustments that are made, and close follow-up to monitor the effects.