Medications That Always Use Actual Body Weight to Calculate Creatinine Clearance

Since the introduction of the Cockcroft-Gault equation to calculate creatinine clearance (CrCl), there has been debate about which weight to use in the equation. The original study published in 1976 used actual body weight, but it mentioned that a correction factor was likely needed for those who are obese.¹

Original Cockcroft-Gault equation:

CrCl = (140−age)∗(weight in kg) ∗ (0.85, if female)

72*SCr

Over the next few decades, the original Cockcroft-Gault equation was modified to use ideal body weight (=2.3 kg*each inch over 5 feet + W; W= 50 kg for males; 45.5 kg for females).²

If a patient’s actual body weight was less than his or her ideal weight, then actual weight should be used. However, if the patient is obese, then a correction is used. The adjusted body weight correction states that if a patient’s actual weight is 30% over his or her ideal body weight, then a 40% correction factor should be applied and that weight should be used in the Cockcroft-Gault equation.³ Corrections of 20% to 40% have been used in practice, but the 40% correction has shown to be the most accurate in estimating true CrCl.

Adjusted body weight = 0.4 (actual body weight - ideal body weight) + ideal body weight

Currently, the vast majority of medications recommend calculation of the Cockcroft-Gault equation to estimate CrCl for dose adjustments based on renal function. The major exceptions include metformin, based on newly published FDA recommendations, and SGLT2 inhibitors.

The calculation hierarchy described above is followed by most electronic medical records when calculating CrCl. However, there is a small minority of medications that recommend using actual body weight in the Cockcroft-Gault formula regardless of extremes (Table).

Table: Medications Using Actual Body Weight When Calculating CrCl

Medication

Brand Name

Dabigatran⁴

Pradaxa

Dofetalide⁵

Tikosyn

Eptifibatide⁶

Integrilin

Pemetrexed⁷

Alimta

Phentermine and topiramate⁸

Qsymia

Rivaroxaban⁹

Xarelto

Zoledronic acid*¹⁰

Reclast

*Only for non-oncologic indications

Underestimation of renal function may occur when using the incorrect weight to calculate CrCl, leading to inappropriate dose reductions. One study retrospectively evaluated 355 patients on dabigtran and rivaroxaban for appropriateness of dosing based on the package insert recommendations for renal insufficiency.¹¹ Most patients in the study were on dabigatran (71.8%) for atrial fibrillation (91%). Renal function was calculated using both ideal and actual body weights of patients.

In the rivaroxaban arm, 85 patients had a CrCl >50 mL/min based on ideal body weight, but that increased to 94 patients when using actual body weight. Nine of those patients inappropriately had their dose reduced to 15 mg daily. In the dabigatran group, 93 patients had a CrCl >30 mL/min utilizing ideal body weight, but that increased to 98 patients when using actual body weight. Two of those patients had inappropriate dose reductions to 75 mg twice-daily.

There was a small amount of patients who necessitated dose reductions and an even smaller number of patients who had inappropriate dose reductions (3.1%). Although those dose reductions may put patients at risk of thrombotic complications, that hasn’t been specifically corroborated in clinical studies.

Overall, pharmacists should be aware of the medications that are outliers in clinical practice to optimize dosing.

References

1. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.

2. Devine BJ. Gentamicin therapy. Drug Intell Clin Pharm. 1974;8:650—655.

3. Winter MA, Guhr KN, Berg GM. Impact of various body weights and serum creatinine concentrations on the bias and accuracy of the Cockcroft-Gault equation. Pharmacotherapy. 2012;32(7):604-612.

4. Pradaxa (dabigatran) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; November 2015.

5. Tikosyn (dofetilide) [prescribing information]. New York, NY: Pfizer; March 2016.

6. Integrilin (eptifibatide) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; August 2014.

7. Alimta (pemetrexed) [prescribing information]. Indianapolis, IN: Eli Lilly and Company; September 2013.

8. Qsymia [prescribing information]. Mountain View, CA: VIVUS Inc; October 2014.

9. Xarelto (rivaroxaban) [prescribing information]. Gurabo, PR: Janssen Pharmaceuticals Inc; May 2016.

10. Reclast (zoledronic acid) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; April 2015.

11. Seig A, Nappi J. Evaluation of dosing practices of rivaroxaban and dabigatran. J Pharm Techn. 2015;(31)4:149-154.