Dosing Patients in Renal Failure



Dosing Patients in Renal Failure


Paul Lewis

James W. Myers



INTRODUCTION

The majority of antibiotics are cleared via renal elimination and will require adjustment for those patients who have renal impairment. Nevertheless, there are several important antibiotics that do not require a dosage adjustment during renal impairment (see Table 56-1).

Renal impairment or failure affects many different pharmacokinetic parameters including absorption, distribution, metabolism, and elimination. Renally eliminated medications do not need to be avoided in patients with impaired renal function; however, a dosing reduction to prevent toxicity may be needed in order to appropriately treat the patient (see Table 56-2). Dosage reduction is usually accomplished by either a decrease in dose or frequency of administration or both.

Hemodialysis also plays a critical role in drug removal. There are multiple methods for administering hemodialysis including intermittent, continuous, and peritoneal dialysis. It is important to determine the type of dialysis as it plays a significant role in drug removal and the need for replacement dosing. It is also important to determine the type of filter being used. For instance, high-flux filters allow for the clearance of larger molecules such as vancomycin warranting a replacement dose after a standard 4-hour session. Peritoneal dialysis uses the body’s own peritoneum as the filter, which does not allow for the passage of larger molecules. Physicians also have the option of dosing antibiotics intravenously or via the intraperitoneal route. This chapter provides a reference for the various dosing strategies for the various degrees of renal dysfunction and for the types of dialysis, including intraperitoneal dosing in peritoneal dialysis.


IMPACT OF RENAL IMPAIRMENT ON PHARMACOKINETICS


Absorption



  • Multiple factors contribute to lower absorption such as nausea, vomiting, gastroparesis, intestinal edema, and delayed gastric emptying.


  • Increases in stomach pH may decrease absorption.


  • Presence of antacids phosphate binders may decrease absorption.


Distribution



  • Protein binding may be limited, increasing the amount of “free drug” at the binding site and at the points of elimination (dialysis or hepatic metabolism).


  • Presence of edema or ascites will increase the volume of distribution of highly protein bound and water soluble medications.


  • Muscle mass loss and dehydration can reduce volume of distribution.









Table 56-1 Antibiotics Without Renal Adjustments



























Amphotericin

Linezolid

Oxacillin


Azithromycin

Metronidazole

Rifampin


Ceftriaxone

Micafungin

Rifabutin


Clindamycin

Minocycline

Rifaximin


Doxycycline

Moxifloxacin

Tigecycline


Itraconazole

Nafcillin

Voriconazole (PO)



Metabolism



  • Uremia can reduce the amount of first-pass metabolism increasing drug levels.


  • Cytochrome P450 isoenzymes 2C6, 2C11, 3C11, 3A1, and 3A2 may be down-regulated due to the accumulation of endogenous inhibitors.


  • Glucuronidation, sulfated conjugation, and oxidation not likely to be affected by uremia


Elimination



  • Drug removal is accomplished by glomerular filtration and tubular secretion.


  • Drugs may also be reabsorbed into circulation.


  • When glomerular filtration decreases, tubular secretion may be enhanced.


  • Renal impairment reduces both glomerular filtration and tubular secretion.


Estimating Renal Function



  • 24-hour urine collection



    • Most accurate, however often impractical to do in the clinical setting


  • Serum creatinine



    • Endogenous amino acid derivative freely filtered by the glomerulus and secreted by the proximal tubules


    • Body composition plays a large role as creatinine is a function of muscle mass.


    • Dietary intake may account for variations seen in different age, race, ethnic, and geographic groups.


    • Age also plays a role as advanced age results in decreased muscle mass and lower creatinine levels.


    • Trimethoprim and cimetidine may inhibit tubular secretion of creatinine causing a falsely elevated serum creatinine.


    • Not useful as a single marker


  • Cockcroft-Gault formula



    • Preferred method for measuring creatinine clearance (CrCl) due to ease of use and historical experience


    • Basis for manufacturer recommendations regarding renal adjustments


    • Of note, Cockcroft-Gault is only valid in “stable” serum creatinine levels!


    • In patients with oliguria or rapidly rising serum creatinine, consider the CrCl to be <10 mL/min.










      Table 56-2 Antibiotic Dosage Adjustments in Renal Impairment not on Dialysisa









































































































































































































































































































      Creatinine Clearance

      Moderate to Severe

      Severe to Life Threatening


      Ampicillin


      CrCl >50 mL/min

      2 g q6h

      2 g q4h


      CrCl 10-50 mL/min

      2 g q8h

      2 g q6h


      CrCl <10 mL/min

      2 g q12h

      2 g q8h


      Ampicillin-sulbactam


      CrCl >30 mL/min

      1.5 g q6h

      3 g q6h


      CrCl 15-29 mL/min

      1.5 g q12h

      3 g q12h


      CrCl <15 mL/min

      1.5 g q24h

      3 g q24h


      Aztreonam


      CrCl >50mL/min

      1 g q8h

      2 g q6-8h


      CrCl 10-50 mL/min

      1 g q12h

      2 g q12h


      CrCl <10 mL/min

      1 q q24h

      2 g q24h


      Cefazolin


      CrCl >35 mL/min

      1 g q8h

      2 g q8h


      CrCl 11-34 mL/min

      500 mg q12h

      1 g q12h


      CrCl <10 mL/min

      500 mg q24h

      1 g q24h


      Cefepime


      CrCl >60 mL/min

      2 g q12h

      2 g q8h


      CrCl 30-60 mL/min

      2 g q24h

      2 g q12h


      CrCl <30 mL/min

      1 g q24h

      2 g q24h


      Cefoxitin


      CrCl >50 mL/min

      1 g q6h

      2 g q6h


      CrCl 30-50 mL/min

      1 g q8h

      2 g q8h


      CrCl 10-30 mL/min

      1 g q12h

      2 g q12h


      CrCl <10 mL/min

      500 mg q24h

      1 g q24h


      Ceftazidime


      CrCl >50 mL/min

      1 g q8h

      2 g q8h


      CrCl 30-50 mL/min

      1 g q12h

      2 g q12h


      CrCl 10-30 mL/min

      1 g q24h

      2 g q24h


      Ciprofloxacin


      CrCl >30 mL/min

      400 mg q12h

      400 mg q8h


      CrCl <30 mL/min

      400 mg q24h

      400 mg q12h


      Colistin


      CrCl >50 mL/min

      2.5 mg/kg q12h

      2.5 mg/kg q12h


      CrCl 30-50 mL/min

      1.5 mg/kg q12h

      1.5 mg/kg q12h


      CrCl 10-30 mL/min

      2.5 mg/kg q24h

      2.5 mg/kg q24h


      CrCl <10 mL/min

      1.5 mg/kg q24h

      1.5 mg/kg q24h


      Daptomycin


      CrCl >30 ml/min

      4 mg/kg q24h

      6-10 mg/kg q24h


      CrCl <30 mL/min

      4 mg/kg q48h

      6-10 mg/kg q48h


      Doripenem


      CrCl >50 mL/min

      500 mg q8h

      500 mg q8h


      CrCl 30-50 mL/min

      250 mg q8h

      250 mg q8h


      CrCl <30 mL/min

      250 mg q12h

      250 mg q12h


      Ertapenem


      CrCl >30 mL/min

      1 g q24h

      1 g q24h


      CrCl <30 mL/min

      500 mg q24h

      500 mg q24h


      Imipenem-cilastatin


      CrCl >70 mL/min

      500 mg q6-8h

      1 g q6-8h


      CrCl 41-70 mL/min

      500 mg q8h

      500 mg q6h


      CrCl 20-40 mL/min

      250 mg q6h

      500 mg q8h


      CrCl <20 mL/min

      250 mg q12h

      500 mg q12h


      Levofloxacin


      CrCl >50 mL/min

      500 mg q24h

      750 mg q24h


      CrCl 20-50 mL/min

      250 mg q24h

      750 mg q48h


      CrCl <20 mL/min

      250 mg q48h

      500 mg q48h


      Meropenem


      CrCl >50 mL/min

      1 g q8h

      2 g q8h


      CrCl 25-50 mL/min

      1 g q12h

      1 g q8h


      CrCl 10-25 mL/min

      500 mg q12h

      1 g q12h


      CrCl <10 mL/min

      500 mg q24h

      1 g q24h


      Penicillin


      CrCl >50 mL/min

      2 million units q4h

      4 million units q4h


      CrCl 10-50 mL/min

      1-1.5 million units q4h

      2-3 million units q4h


      CrCl <10 mL/min

      1 million units q6h

      2 million units q6h


      Piperacillin-tazobactam


      CrCl >40 mL/min

      3.375 g q6h

      4.5 g q6h


      CrCl 20-40 mL/min

      2.25 g q6h

      3.375 g q6h


      CrCl <20 mL/min

      2.25 g q8h

      2.25 g q6h


      Telavancin


      CrCl >50 mL/min

      10 mg/kg q24h

      10 mg/kg q24h


      CrCl 30-50 mL/min

      7.5 mg/kg q24h

      7.5 mg/kg q24h


      CrCl <30 mL/min

      10 mg/kg q48h

      10 mg/kg q48h


      Ticarcillin-clavulanic acid


      CrCl >60 mL/min

      3.1 g q6h

      3.1 g q4h


      CrCl 30-60 mL/min

      2 g q4-6h

      2 g q4h


      CrCl 10-30 mL/min

      2 g q8-12h

      2 g q8h


      CrCl <10 mL/min

      2 g q12h

      2 g q12h


      Trimethoprim-sulfamethoxazole


      CrCl >30

      5 mg/kg q12h

      5 mg/kg q8h


      CrCl 10-30

      2.5 mg/kg q12h

      5 mg/kg q12h


      CrCl <10

      Avoid

      2.5 mg/kg q12h


      a Vancomycin and aminoglycosides are discussed in the therapeutic drug monitoring chapter.

      Only gold members can continue reading. Log In or Register to continue

      Related posts:

      Default ThumbnailGonorrhea Default ThumbnailRocky Mountain Spotted Fever Default ThumbnailInfective Endocarditis: Treatment and Prophylaxis Default ThumbnailBartonella Default ThumbnailAntibiotic Dosing in Obesity Default ThumbnailInfections in Pregnancy and the Perinatal Period

      Stay updated, free articles. Join our Telegram channel
Tags:
Jun 22, 2016 | Posted by in INFECTIOUS DISEASE | Comments Off on Dosing Patients in Renal Failure

Full access? Get Clinical Tree
Get Clinical Tree app for offline access