Safety and efficiency of molnupiravir for COVID-19 patients with advanced chronic kidney disease

Article information

Kidney Res Clin Pract. 2023;42(2):275-278

Publication date (electronic) : 2023 March 31

doi : https://doi.org/10.23876/j.krcp.22.194

Inès Dufour¹, Arnaud Devresse¹, Anais Scohy², Caroline Briquet³, Hélène Georgery¹, Philippe Delaey¹, Julien De Greef⁴, Eric Goffin¹, Laura Labriola^,1

¹Department of Nephrology, Saint-Luc University Clinics, Brussels, Belgium

²Department of Microbiology, Saint-Luc University Clinics, Brussels, Belgium

³Department of Pharmacy, Saint-Luc University Clinics, Brussels, Belgium

⁴Department of Internal Medicine and Infectious Disease, Saint-Luc University Clinics, Brussels, Belgium

Correspondence: Laura Labriola Department of Nephrology, Cliniques Universitaires Saint-Luc, Av. Hippocrate 10, Brussels 1200, Belgium. E-mail: laura.labriola@uclouvain.be

Received 2022 August 23; Revised 2022 October 13; Accepted 2022 October 27.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is particularly life threatening in patients who are immunocompromised, including those with advanced chronic kidney disease (CKD) [1,2]. Despite the implementation of a third dose of a messenger RNA (mRNA) vaccine, the efficacy of SARS-CoV-2 vaccination on humoral and cellular immunities is reduced in the population with CKD, resulting in an increased incidence of severe infection and mortality, including in fully vaccinated patients [3].

In this context, several antiviral therapies or monoclonal antibodies are being investigated for treatment of COVID-19. These drugs prevent viral replication through various mechanisms, including neutralization, blocking SARS-CoV-2 entry, and inhibiting RNA polymerase or proteases activity [4,5]. However, patients with CKD are frequently excluded from clinical trials evaluating new drugs.

Although sotrovimab and casirivimab/imdevimab have been shown to confer satisfactory protection against the COVID-19 Delta variant, they have limited neutralizing activity against the Omicron variant [4]. Remdesivir, nirmatrelvir/ritonavir, bebtelovimab, and molnupiravir seem to be effective against the Omicron variant [5]. U.S. Food and Drug Administration product labels do not recommend remdesivir or nirmatrelvir/ritonavir in patients with an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 m² due to a lack of data concerning the risk of drug accumulation in this population. Indeed, nirmatrelvir and one of the excipients contained in remdesivir (betadex sulfobutyl ether sodium) are renally cleared and can accumulate in patients with abnormal kidney function. The appropriate dose for patients with severe renal impairment has not been determined. Bebtelovimab is only available in the United States. Thus, molnupiravir is the only antiviral drug that could potentially be used for CKD patients with the COVID-19 Omicron variant outside of the United States. Molnupiravir is an inhibitor of the RNA-dependent RNA polymerase of SARS-CoV-2. Although a phase III double-blind, placebo-controlled study of molnupiravir as an oral treatment for COVID-19 in nonhospitalized adults (MOVe-OUT) showed good efficacy, patients with eGFR of <30 mL/min or on dialysis were excluded [6]. To our knowledge, this is the first report on the efficacy and safety of molnupiravir in advanced CKD patients.

Three patients were on maintenance hemodialysis, one had received a transplant and had CKD G4 (eGFR, 18 mL/min/1.73 m²), and one had CKD G5 (eGFR, 11 mL/min/1.73 m²) (Table 1). Patients 1, 2, and 4 were under immunosuppressive therapy (heart transplantation, renal transplantation, and treatment of minimal change disease, respectively). All five were fully vaccinated (four doses of the mRNA BNT162b2 vaccine [Pfizer-BioNTech]). They received molnupiravir at a dosage of 800 mg twice daily for 5 days (given after hemodialysis on dialysis day) for mild-to-moderate COVID-19. Quantitative reverse transcription polymerase chain reaction was performed on nasopharyngeal swabs at diagnosis, on day 6 or 7 to evaluate the time to clearance of the virus, and on day 13 for patients 4 and 5 (Fig. 1). Three patients showed <1,000 copies/mL at day 6 or 7. Patients 4 and 5 had results of 1,685 and 2,071 copies/mL on day 13, respectively, and rapid symptom resolution. No adverse effects were observed in any patient. Renal function remained stable in the two CKD patients who were not on dialysis (Table 1). One month after treatment, four patients were entirely asymptomatic and feeling well. Patient 1 still reported tiredness and loss of appetite. None of the five patients experienced delayed immune events or early recurrence of SARS-CoV-2 infection.

Table 1.

Baseline and COVID-19 characteristics of patients treated with molnupiravir.

Figure 1.

Evolution of the SARS-CoV-2 viral load on nasopharyngeal swabs.

SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Molnupiravir is a prodrug that is metabolized to the ribonucleoside analogue N-hydroxycytidine (NHC). NHC is distributed into cells where it is incorporated into viral RNA by the viral RNA polymerase, which inhibits replication [7]. NHC is eliminated by cellular metabolism to uridine and/or cytidine through the same pathways involved in endogenous pyrimidine metabolism [8]. Renal clearance is not a meaningful route of elimination for NHC. For these reasons, no dose adjustments in patients with any degree of kidney impairment are recommended on the product label [7,8].

Molnupiravir is a safe drug with no contraindications (except during pregnancy and in patients aged <18 years because it may affect bone and cartilage growth). Side effects are limited; the most common (incidence ≥ 1%) include diarrhea, nausea, and dizziness [6]. No drug interactions have been identified (unlike for nirmatrelvir-ritonavir); although ritonavir is a potent CYP3A4 inhibitor and an inducer of other cytochrome p450 substances, oral administration allows treatment outside the hospital, while remdesivir or bebtelovimab requires an intravenous route.

In conclusion, this real-life observational study reported the safety of molnupiravir use in advanced CKD and its relative effectiveness on symptoms and virus clearance.