Dose-Dependent Hyperkalemia Among Hospitalized, HIV-Infected Patients Receiving Sulfamethoxazole/Trimethoprim

Abstract

Background: Sulfamethoxazole-trimethoprim (SXT) therapy is commonly used in HIV-infected patients and is associated with hyperkalemia and elevated serum creatinine (SCr). Objective: The purpose of this study was to examine the frequency of hyperkalemia and elevated SCr in hospitalized, HIV-infected patients receiving SXT. Methods: This was a retrospective, single-center cohort study. HIV-infected hospitalized patients receiving a minimum of 3 consecutive days of SXT were included. Patients were grouped according to high dose (≥10 mg/kg/d) and low dose (<10 mg/kg/d) trimethoprim. The primary end point was the frequency of hyperkalemia, severe hyperkalemia, and elevated SCr. Secondary end points included an evaluation of concomitant potassium-altering medications and concomitant nephrotoxic drugs. Results: A total of 100 consecutive patients were selected from all possible patients who met inclusion criteria. Overall, 47 patients experienced at least 1 adverse drug event (ADE) of either hyperkalemia or increased SCr, with 20 patients experiencing these ADEs in the low-dose group and 27 patients experiencing these ADEs in the high-dose group ( P = 0.229). The ADEs of hyperkalemia or increased SCr occurred after a shorter period (5.5 vs 8.7 days) in the high-dose group ( P = 0.049). Overall frequency of elevated SCr was 24% and of elevated serum K was 36%. Hyperkalemia requiring a therapeutic intervention occurred in 12 patients in the high-dose group compared with 2 in the low-dose group ( P = 0.009). Conclusion and Relevance: Rates of elevated SCr and hyperkalemia in hospitalized HIV-infected patients receiving SXT are significant. Hyperkalemia requiring intervention is more common in patients receiving high-dose SXT.

Epidemiology, prognosis and management of potassium disorders in Covid‐19

“…37 Trimethoprim-sulfamethoxazole which is usually given in high dose for Pneumocystis jirovecii pneumonia in immunocompromised patients is an important cause of hyperkalemia. 38 Elevated serum potassium levels above 5 mmol/L was reported in 24% and 48% of HIV-infected patients receiving low-and high-dose trimethoprim-sulfamethoxazole, respectively, such that 14% required therapeutic intervention for addressing the complications of hyperkalemia. 38…”

“…38 Elevated serum potassium levels above 5 mmol/L was reported in 24% and 48% of HIV-infected patients receiving low-and high-dose trimethoprim-sulfamethoxazole, respectively, such that 14% required therapeutic intervention for addressing the complications of hyperkalemia. 38…”

“…HIV positive patients are at increased risk of developing hyperkalemia 37 . Trimethoprim‐sulfamethoxazole which is usually given in high dose for Pneumocystis jirovecii pneumonia in immunocompromised patients is an important cause of hyperkalemia 38 38 …”

Low-dose trimethoprim-sulfamethoxazole for the treatment ofPneumocystis jiroveciipneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial

“…Higher doses of TMP-SMX are associated with hypersensitivity reactions, drug-induced liver injury, cytopenias and renal failure. [19][20][21][22][23][24][25][26][27] A daily dose of >15 mg/kg is an independent predictor of adverse drug events (ADEs) 28 with the frequency of haematological and renal adverse events increasing in a dose-dependent manner. 29 ADEs have been reported among 20%-60% [30][31][32][33][34][35][36] of patients and up to 40% have discontinued therapy due to drug intolerance in previous randomised controlled trials (RCTs).…”

“…Current guidelines from Centers for Disease Control and Prevention, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America and the American Society of Transplantation15–18 recommend weight-based trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 15–20 mg/kg/day of the TMP component as the standard of care. Higher doses of TMP-SMX are associated with hypersensitivity reactions, drug-induced liver injury, cytopenias and renal failure 19–27. A daily dose of >15 mg/kg is an independent predictor of adverse drug events (ADEs)28 with the frequency of haematological and renal adverse events increasing in a dose-dependent manner 29.…”