Does posaconazole cause Acute Kidney Injury (AKI)?

From the Guidelines

Posaconazole does not commonly cause Acute Kidney Injury (AKI).

Posaconazole Toxicity Profile

• The study 1 suggests that posaconazole is generally well tolerated, with serious adverse events, primarily liver toxicity, being rare.
• There is no mention of posaconazole causing Acute Kidney Injury (AKI) in the provided evidence.
• However, it is noted that the intravenous formulation of voriconazole, another azole, may accumulate in patients with renal dysfunction due to its cyclodextrin vehicle, but this is not mentioned for posaconazole.
• QTc prolongation is a potential concern with posaconazole, as with other azoles, which may be exacerbated by combination with other drugs.

Clinical Implications

• In real-life clinical practice, posaconazole can be used with caution, monitoring for potential drug-drug interactions and QTc prolongation, but Acute Kidney Injury (AKI) is not a commonly associated adverse event.
• As with any medication, it is essential to weigh the benefits and risks of posaconazole and monitor patients closely for any potential adverse effects.

From the FDA Drug Label

1. 6 Renal Impairment Following single-dose administration of 400 mg of the Noxafil ®oral suspension, there was no significant effect of mild (eGFR: 50-80 mL/min/1.73 m 2, n=6) or moderate (eGFR: 20-49 mL/min/1. 73 m 2, n=6) renal impairment on posaconazole pharmacokinetics; therefore, no dose adjustment is required in patients with mild to moderate renal impairment.

The FDA drug label does not directly answer the question of whether posaconazole causes Acute Kidney Injury (AKI). The label discusses the effect of renal impairment on posaconazole pharmacokinetics, but it does not provide information on the potential of posaconazole to cause AKI. 2

From the Research

Posaconazole and Acute Kidney Injury (AKI)

• Posaconazole is an orally administered second-generation triazole antifungal agent that has been associated with renal disorders, including AKI, in some cases 3, 4.
• The incidence of renal disorders with posaconazole is considered uncommon, occurring in approximately 0.1-1% of patients 3.
• Studies have reported cases of AKI in patients treated with posaconazole, including a case of thrombotic microangiopathy in a patient with mucormycosis 4.
• However, other studies have found that posaconazole is generally well tolerated and does not require dosage adjustments in patients with varying degrees of renal disease 5.
• The mechanisms of antimicrobial-induced AKI, including those caused by posaconazole, are not fully understood but may involve acute interstitial nephritis, acute tubular necrosis, and other forms of renal injury 6.

Risk Factors for Posaconazole-Induced AKI

• Pre-existing chronic kidney disease may increase the risk of AKI in patients treated with posaconazole 6.
• Concomitant use of other medications with nephrotoxic potential may also increase the risk of AKI in patients treated with posaconazole 6.
• Patients with severe COVID-19 may be at increased risk of developing AKI while taking posaconazole due to altered immune regulation and increased inflammation 4.

Monitoring and Prevention of Posaconazole-Induced AKI

• Regular monitoring of renal function may be necessary for patients on posaconazole to facilitate early identification of AKI 3.
• Early recognition and prevention of AKI are crucial to mitigating the risk of morbidity and mortality in patients treated with posaconazole 6.