PharmtoExamTable (Part 2): Why should sulfamethoxazole/trimethoprim (Bactrim) be used with caution in patients with renal impairment or those on dialysis?

This #PharmToExamTable post was authored by Eric Hiatt, PharmD Candidate (2025) at the UNMC College of Pharmacy, and explores Bactrim’s use in those with impaired renal function.

(Content reviewed by Jenna Preusker, PharmD, BCPS, BCIDP)


Recall from Part 1:

Impact of sulfamethoxazole/trimethoprim on Renal FunctionIn patients with renal impairment, administration of sulfamethoxazole/trimethoprim has been shown to have a significant incidence of acute kidney injury (AKI) 
Mechanism of sulfamethoxazole/trimethoprim-Induced AKISulfamethoxazole’s metabolite, N-acetyl-sulfamethoxazole (NASM), may form crystalline structures in acidic urine, causing renal damage in the form of AKI.

In addition to increased risk of AKI, patients with renal impairment are more likely to experience electrolyte abnormalities while taking sulfamethoxazole/trimethoprim, particularly hyperkalemia and hyponatremia. The electrolyte abnormalities are believed to be attributed to the trimethoprim component of sulfamethoxazole/trimethoprim through an amiloride-like effect.4,5 Trimethoprim is structurally like amiloride, a diuretic known to retain potassium and excrete sodium in the kidneys. Furthermore, trimethoprim has been shown to inhibit the same sodium transport channels that amiloride inhibits reversibly. In animal studies, intravenous trimethoprim was shown to decrease potassium and increase sodium urinary excretion by 40% and 46%, respectively.These electrolyte abnormalities are reported to be more common with high doses of sulfamethoxazole/trimethoprim in non-renally impaired patients indicating these effects are dose dependent.5

In patients with renal impairment, sulfamethoxazole/trimethoprim can accumulate, resulting in common daily doses causing these electrolyte abnormalities.5 In the case of sulfamethoxazole/trimethoprim, both drugs are primarily eliminated through the kidneys causing accumulation in renal impairment. In severe renal impairment, the half-life of both drugs can significantly increase from 11 and 9 hours each to 45-60 hours. The recommended dose adjustment to prevent accumulation of sulfamethoxazole/trimethoprim occurs when the patient’s creatinine clearance is <30 ml/min.6

CrClDose
CrCl < 30 ml/minStandard dose
CrCl 15-30 ml/minReduce dose by half
CrCl < 15 ml/minUse not recommended 
The FDA recommendations for the adjustment of sulfamethoxazole/trimethoprim based on renal impairment

Notably, the FDA does not recommend sulfamethoxazole/trimethoprim use in patients with CrCl < 15 ml/min; however, it may be the only option available. 

CrClDose
CrCl < 30 ml/minStandard dose
CrCl 15-30 ml/minReduce dose by half
CrCl < 15 ml/minCrCl <15: Adjust to 25-50% of the total daily dose for indication. Use caution and monitor.
HemodialysisDose as CrCl < 15 ml/min, administer after HD on dialysis days 
Nebraska Medicine renal dose adjustment guidelines7

Alternative dosing based on type of dialysis based off the trimethoprim component:

Dialysis Trimethoprim Based Dose IV
Hemodialysis2.5-5 mg/kg every 12 hours; administered after hemodialysis
CVVH2.5-7.5 mg/kg every 12 hours
CVVHD4-5 mg/kg every 6-8 hours
CVVHDF4-5 mg/kg every 6-8 hours
Alternative Dialysis regimens8

Final Take Home Points:

Impact of sulfamethoxazole/trimethoprim on Renal FunctionIn patients with renal impairment, administration of sulfamethoxazole/trimethoprim has been shown to have a significant incidence of acute kidney injury (AKI) 
Mechanism of sulfamethoxazole/trimethoprim-Induced AKISulfamethoxazole’s metabolite, N-acetyl-sulfamethoxazole (NASM), may form crystalline structures in acidic urine, causing renal damage in the form of AKI.
Electrolyte Abnormalities from sulfamethoxazole/trimethoprimPatients with renal impairment on sulfamethoxazole/trimethoprim may develop hyperkalemia and hyponatremia due to trimethoprim’s effect on sodium and potassium transport. These effects are dose-dependent and more likely in patients with impaired renal function due to drug accumulation.
Dosing Adjustments in Renal ImpairmentSulfamethoxazole/trimethoprim’s elimination is primarily renal, with a prolonged half-life in severe renal impairment. FDA dosing adjustments based on CrCl levels: CrCl >30 mL/min: standard dose, CrCl 15-30 mL/min: reduce dose by half, CrCl <15 mL/min: use not recommended, but may be necessary

References:

1. Fraser TN, Avellaneda AA, Graviss EA, et al. Acute kidney injury associated with trimethoprim/sulfamethoxazole. Journal of Antimicrobial Chemotherapy, 2012; 67(5), 1271–1277. https://doi.org/10.1093/jac/dks030

2. Azencot R, Saint-Jacques C, Haymann JP, et al. Sulfamethoxazole-induced crystal nephropathy: Characterization and prognosis in a case series. Scientific Reports, 2024; 14, 6078. https://doi.org/10.1038/s41598-024-56322-9

3. Perazella MA. Crystal-induced acute renal failure. The American Journal of Medicine, 1999; 106(4), 459–465. https://doi.org/10.1016/S0002-9343(99)00041-8

4. Perazella MA. Trimethoprim-Induced Hyperkalaemia. Drug Safety, 2000; 22(3), 227–236. https://doi.org/10.2165/00002018-200022030-00006

5. Mori H, Kuroda Y, Imamura S, et al. Hyponatremia and/or Hyperkalemia in Patients Treated with the Standard Dose of Trimethoprim-sulfamethoxazole. Internal Medicine, 2003; 42(8), 665–669. https://doi.org/10.2169/internalmedicine.42.665

6. Patel RB, Welling PG. Clinical Pharmacokinetics of Co-trimoxazole (trimethoprim-sulphamethoxazole). Clinical Pharmacokinetics, 1980; 5(5), 405–423. https://doi.org/10.2165/00003088-198005050-00001

7. Nebraska Medicine renal guidelines for antibiotics. Accessed May 2024. https://www.unmc.edu/intmed/_documents/id/asp/dose-nm-anti-infective-renal-dosing-guidelines.pdf

8. Golightly LK, Teitelbaum I, Kiser, TH, et al. Renal Pharmacotherapy: Dosage Adjustment of Medications Eliminated by the Kidneys. Springer New York; 2013. https://doi.org/10.1007/978-1-4614-5800-5

Leave a comment

Your email address will not be published. Required fields are marked *

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

This site uses Akismet to reduce spam. Learn how your comment data is processed.

dkwWSbPjZJO Fg yhqJxFP scti