Bezafibrate SR in patients with impaired renal function
Insights from the Clinical Department: Dr. Hen Popilski, PhD, Dr. Shiri Guy-Alfandary, PharmD.
Alert Category: Renal module
Case Description: Bezafibrate sustained release formulation in a patient with impaired renal function (eGFR <60 ml/min).
Clinical Rationale:
Bezafibrate is primarily eliminated from the body through renal excretion (95%). In patients with impaired renal function, its half-life is prolonged, leading to drug accumulation in the blood. This condition may increase the risk of rhabdomyolysis. Additionally, studies have shown that bezafibrate accumulation causes a dose-dependent deterioration in renal function (elevated serum urea and creatinine) without evidence of tubular damage or signs of inflammation. This deterioration is reversible upon dose adjustment or discontinuation of fibrate therapy, with creatinine levels returning to baseline.
Recommendation
Evaluate the justification for fibrate therapy, and if necessary, recommend switching to an immediate-release formulation while adjusting the dose according to renal function, as detailed in Table 1. We recommend using this opportunity to reassess the necessity of fibrate therapy, particularly in cases where baseline TG levels did not initially warrant its addition. Consideration should also be given to potent statin therapy, such as atorvastatin or rosuvastatin, which may significantly reduce TG levels.
It is important to note that among potent statins, dose adjustment is also required for rosuvastatin in patients with impaired renal function. Specifically, for CrCl <30 ml/min, the maximum approved daily dose is 10 mg, as per FDA guidelines and the Israeli dyslipidemia treatment guidelines. However, this differs from Israeli drug labeling, which is even more restrictive.
Additionally, when prescribing statins, attention should be given to drug interactions, which may also limit the maximum permissible dose when used in combination (see Table 2).
References:
Bezafibrate sustained-release prescribing information leaflet. Available at: https://israeldrugs.health.gov.il/
Bezafibrate immediate release prescribing information leaflet. Available at: https://israeldrugs.health.gov.il/
Charach G, Grosskopf I, Rotmensch HH, Kitzis I, Weintraub M. Bezafibrates cause moderate, reversible impairment in renal function in patients without prior renal disease. Nephron Clin Pract. 2005;100(4):c120-5. doi: 10.1159/000085291. Epub 2005 Apr 20. PMID: 15849478.
Zingerman B, Ziv D, Feder Krengel N, Korzets A, Matok I. Cessation of Bezafibrate in patients with chronic kidney disease improves renal function. Sci Rep. 2020 Nov 13;10(1):19768. doi: 10.1038/s41598-020-76861-1. PMID: 33188240; PMCID: PMC7666122.
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