In this episode, I’ll discuss why remdesivir is not indicated in patients with an eGFR below 30 mL/min.
Remdesivir has recently been approved for the treatment of COVID-19 in hospitalized patients. The prescribing information states that it is not recommended in patients with eGFR less than 30 mL per minute.
The reason for this restriction is not due to the accumulation of remdesivir, rather it is due to an excipient that can accumulate in renal insufficiency. This excipient is betadex sulfobutyl ether sodium, which is better known by its trade name, Captisol.
Captisol is a cyclodextrin compound that improves the solubility of numerous medications, allowing them to be delivered as IV formulations.
Captisol was originally designed to replace a more toxic excipient, polysorbate 80, in the IV formulation of amiodarone. Once developed, it was licensed to other manufacturers and is present in the Nexterone brand of IV amiodarone and intravenous voriconazole.
Captisol has been associated with hepatic and renal toxicity in animals at high doses, and that forms the basis for concern in humans.
IV voriconazole also carries a similar warning about its use in patients with a very low eGFR due to accumulation concerns of Captisol. Interestingly, IV voriconazole also carries a caveat to the warning against use in low eGFR that it should not be used “…unless an assessment of the benefit/risk to the patient justifies the use of intravenous voriconazole.” No such caveat appears in the remdesivir prescribing information, however, even though both medications contain nearly identical amounts of Captisol (~3g).
Data exists that patients undergoing CVVH eliminate Captisol at rates equivalent to a patient with normal renal function, so theoretically if a patient had accumulated Captisol it could be removed by CVVH.
Listener “Pharmacy Sunish” sent in this retrospective chart review study that did not show renal or hepatic toxicity with remdesivir use in patients with a clcr less than 30 mL/min. The authors concluded:
Remdesivir administration was not significantly associated with increased end of treatment AKI in patients with an eCrCl < 30mL/min compared to patients with an eCrCl ≥ 30mL/min.
To access my free download area with 20 different resources to help you in your practice, go to pharmacyjoe.com/free.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.