Real-World Use of Molnupiravir in the Treatment of Outpatients with SARS-CoV-2 Infection—A Patient Profile Based on the Experience of a Tertiary Infectious Disease Center
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Molnupiravir—Data on Use in Our Clinical Practice
3.2. Comparison of Real-World Data with Clinical Trial Data
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Booth, A.; Reed, A.B.; Ponzo, S.; Yassaee, A.; Aral, M.; Plans, D.; Labrique, A.; Mohan, D. Population risk factors for severe disease and mortality in COVID-19: A global systematic review and meta-analysis. PLoS ONE 2021, 16, e0247461. [Google Scholar] [CrossRef]
- Bentivegna, M.; Hulme, C.; Ebell, M.H. Primary Care Relevant Risk Factors for Adverse Outcomes in Patients with COVID-19 Infection: A Systematic Review. J. Am. Board. Fam. Med. 2021, 34, S113–S126. [Google Scholar] [CrossRef]
- Wang, L.; Yang, L.M.; Pei, S.F.; Chong, Y.Z.; Guo, Y.; Gao, X.L.; Tang, Q.Y.; Li, Y.; Feng, F.M. CRP, SAA, LDH, and DD predict poor prognosis of coronavirus disease (COVID-19): A meta-analysis from 7739 patients. Scand. J. Clin. Lab. Investig. 2021, 81, 679–686. [Google Scholar] [CrossRef]
- Zhang, J.J.Y.; Lee, K.S.; Ang, L.W.; Leo, Y.S.; Young, B.E. Risk factors for severe disease and efficacy of treatment in patients infected with COVID-19: A systematic review, meta-analysis, and meta-regression analysis. Clin. Infect. Dis. 2020, 71, 2199–2206. [Google Scholar] [CrossRef]
- Bayrak, V.; Senturk Durukan, N.; Demirer Aydemir, F.; Ergan, B.; Gezer, N.S.; Eren Kutsoylu, O.O.; Gokmen, A.N.; Savran, Y. Risk factors associated with mortality in intensive care COVID-19 patients: The importance of chest CT score and intubation timing as risk factors. Turk. J. Med. Sci. 2021, 51, 1665–1674. [Google Scholar] [CrossRef]
- Hashemian, S.M.R.; Pourhanifeh, M.H.; Hamblin, M.R.; Shahrzad, M.K.; Mirzaei, H. RdRp inhibitors and COVID-19: Is molnupiravir a good option? Biomed. Pharmacother. 2022, 146, 112517. [Google Scholar] [CrossRef]
- Masyeni, S.; Iqhrammullah, M.; Frediansyah, A.; Nainu, F.; Tallei, T.; Emran, T.B.; Ophinni, Y.; Dhama, K.; Harapan, H. Molnupiravir: A lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2—A narrative review. J. Med. Virol. 2022, 94, 3006–3016. [Google Scholar] [CrossRef]
- Kabinger, F.; Stiller, C.; Schmitzova, J.; Dienemann, C.; Kokic, G.; Hillen, H.S.; Hobartner, C.; Cramer, P. Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis. Nat. Struct. Mol. Biol. 2021, 28, 740–746. [Google Scholar] [CrossRef]
- Imran, M.; Kumar Arora, M.; Asdaq, S.M.B.; Khan, S.A.; Alaqel, S.I.; Alshammari, M.K.; Alshehri, M.M.; Alshrari, A.S.; Mateq Ali, A.; Al-Shammeri, A.M.; et al. Discovery, Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19. Molecules 2021, 26, 5795. [Google Scholar] [CrossRef]
- COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available online: https://www.covid19treatmentguidelines.nih.gov/ (accessed on 14 August 2022).
- Jayk Bernal, A.; Gomes da Silva, M.M.; Musungaie, D.B.; Kovalchuk, E.; Gonzalez, A.; Delos Reyes, V.; Martin-Quiros, A.; Caraco, Y.; Williams-Diaz, A.; Brown, M.L.; et al. Molnupiravir for oral treatment of COVID-19 in non-hospitalized patients. N. Engl. J. Med. 2022, 386, 509–520. [Google Scholar] [CrossRef]
- ORDIN nr. 260 din 4 februarie 2022 Privind Modificarea Anexei la Ordinul Ministrului Sănătății nr. 487/2020 Pentru Aprobarea Protocolului de Tratament al Infecției cu Virusul SARS-CoV-2; Ministry of Health: Bucharest, Romania, 2022.
- Centrul Național de Supraveghere și Control al Bolilor Transmisibile. Definitiile de caz Pentru Sindromul Respirator Acut cu Noul Coronavirus (COVID-19). Available online: http://cnscbt.ro/index.php/3071-definitii-de-caz-si-recomandari-de-prioritizare-a-testarii-pentru-covid-19-actualizare-18-03-2022 (accessed on 15 August 2022).
- Centrul Național de Supraveghere și Control al Bolilor Transmisibile. Informare Privind Cazurile de COVID-19 Confirmate cu Variante ale SARS-CoV-2 Care Determină îngrijorare (VOC). Available online: https://insp.gov.ro/download/CNSCBT/docman-files/Coronavirus%20nCoV/analiza_cazuri_confirmate_covid-19/S-13_Informare-cazuri-cu-variante-care-determina-ingrijorare-VOC.pdf (accessed on 15 August 2022).
- Johnson, M.G.; Puenpatom, A.; Moncada, P.A.; Burgess, L.; Duke, E.R.; Ohmagari, N.; Bassetti, M.; Bhagani, S.; Ghosn, J.; Zhang, Y.; et al. Effect of molnupiravir on biomarkers, respiratory interventions, and medical services in COVID-19: A randomized, placebo-controlled trial. Ann. Intern. Med. 2022, 175, 1126–1134. [Google Scholar] [CrossRef]
- De Vito, A.; Colpani, A.; Bitti, A.; Zauli, B.; Meloni, M.C.; Fois, M.; Denti, L.; Bacciu, S.; Marcia, C.; Maida, I.; et al. Safety and efficacy of molnupiravir in SARS-CoV-2-infected patients: A real-life experience. J. Med. Virol. 2022. [Google Scholar] [CrossRef]
- Streinu-Cercel, A.; Sandulescu, O.; Miron, V.D.; Paraschiv, S.; Casangiu, C.; Hohan, R.; Banica, L.; Surleac, M.; Streinu-Cercel, A. Undetected omicron transmission in Romania-report of the first detected case of locally acquired omicron infection and complete epidemiological investigation. Diagnostics 2022, 12, 348. [Google Scholar] [CrossRef]
- Metlay, J.P.; Armstrong, K.A. Clinical decision making during the COVID-19 pandemic. Ann. Intern. Med. 2021, 174, 691–693. [Google Scholar] [CrossRef]
- Tobin, L.; de Almedia Neto, A.C.; Wutzke, S.; Patterson, C.; Mackson, J.; Weekes, L.; Williamson, M. Influences on the prescribing of new drugs. Aust. Fam. Physician 2008, 37, 78–80. [Google Scholar]
- Jones, M.I.; Greenfield, S.M.; Bradley, C.P. Prescribing new drugs: Qualitative study of influences on consultants and general practitioners. BMJ 2001, 323, 378–381. [Google Scholar] [CrossRef]
- Schaut, M.; Schaefer, M.; Trost, U.; Sander, A. Integrated antibiotic clinical decision support system (CDSS) for appropriate choice and dosage: An analysis of retrospective data. Germs 2022, 12, 203–213. [Google Scholar] [CrossRef]
- Curtis, C.E.; Al Bahar, F.; Marriott, J.F. The effectiveness of computerised decision support on antibiotic use in hospitals: A systematic review. PLoS ONE 2017, 12, e0183062. [Google Scholar] [CrossRef]
- Havers, F.; Thaker, S.; Clippard, J.R.; Jackson, M.; McLean, H.Q.; Gaglani, M.; Monto, A.S.; Zimmerman, R.K.; Jackson, L.; Petrie, J.G.; et al. Use of influenza antiviral agents by ambulatory care clinicians during the 2012–2013 influenza season. Clin. Infect. Dis. 2014, 59, 774–782. [Google Scholar] [CrossRef]
- Cizeron, A.; Saunier, F.; Gagneux-Brunon, A.; Pillet, S.; Cantais, A.; Botelho-Nevers, E. Low rate of oseltamivir prescription among adults and children with confirmed influenza illness in France during the 2018–2019 influenza season. J. Antimicrob. Chemother. 2021, 76, 1057–1062. [Google Scholar] [CrossRef]
- Miron, V.D.; Bar, G.; Filimon, C.; Craiu, M. From COVID-19 to Influenza-Real-Life Clinical Practice in a Pediatric Hospital. Diagnostics 2022, 12, 1208. [Google Scholar] [CrossRef]
- Udwadia, Z.F.; Singh, P.; Barkate, H.; Patil, S.; Rangwala, S.; Pendse, A.; Kadam, J.; Wu, W.; Caracta, C.F.; Tandon, M. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int. J. Infect. Dis. 2021, 103, 62–71. [Google Scholar] [CrossRef]
- Hung, D.T.; Ghula, S.; Aziz, J.M.A.; Makram, A.M.; Tawfik, G.M.; Abozaid, A.A.; Pancharatnam, R.A.; Ibrahim, A.M.; Shabouk, M.B.; Turnage, M.; et al. The efficacy and adverse effects of favipiravir on patients with COVID-19: A systematic review and meta-analysis of published clinical trials and observational studies. Int. J. Infect. Dis. 2022, 120, 217–227. [Google Scholar] [CrossRef]
Characteristics | Number | Percentage (%) |
---|---|---|
Demographic data | ||
Male sex | 26 | 56.5 |
Female sex | 20 | 43.5 |
Median age (years) | 48.5 (IQR: 37.8, 67.0) | |
Chronic condition | ||
Obesity | 14 | 30.4 |
Cardiovascular disease | 13 | 28.3 |
Asthma | 2 | 4.3 |
COPD | 1 | 2.2 |
Neoplasia | 5 | 10.9 |
Chronic kidney disease | 0 | 0.0 |
Autoimmune disease | 1 | 2.2 |
Diabetes mellitus | 7 | 15.2 |
Other | 3 | 6.5 |
1 chronic condition | 15 | 60.0 * |
2 chronic conditions | 7 | 28.0 * |
3 chronic conditions | 3 | 12.0 * |
COVID-19 vaccination status | ||
2 doses mRNA vaccine | 11 | 29.0 |
3 doses mRNA vaccine | 25 | 65.8 |
1 dose viral vector vaccine ** | 1 | 2.6 |
2 doses viral vector vaccine | 1 | 2.6 |
Symptoms | Male (N = 26) | Female (N = 20) | p-Value | Vaccinated (N = 36) | Unvaccinated (N = 8) | p-Value | Total (N = 46) |
---|---|---|---|---|---|---|---|
Cough | 15 (57.7) | 17 (85.0) | 0.046 | 25 (65.8) | 7 (87.5) | 0.225 | 32 (69.6) |
Headache | 10 (38.5) | 14 (70.0) | 0.034 | 19 (52.8) | 5 (62.5) | 0.520 | 24 (52.2) |
Sore throat | 13 (50.0) | 12 (60.0) | 0.500 | 23 (63.9) | 2 (25.0) | 0.067 | 25 (54.3) |
Myalgia | 9 (34.6) | 8 (40.0) | 0.708 | 11 (30.1) | 6 (75.0) | 0.019 | 17 (37.0) |
Fever | 9 (34.6) | 8 (40.0) | 0.708 | 13 (34.2) | 4 (50.0) | 0.400 | 17 (37.0) |
Rhinorrhea | 8 (30.8) | 9 (45.0) | 0.322 | 13 (34.2) | 4 (50.0) | 0.400 | 17 (37.0) |
Malaise | 5 (19.2) | 5 (25.0) | 0.638 | 6 (15.8) | 4 (50.0) | 0.033 | 10 (21.7) |
Chest pain | 2 (7.7) | 1 (5.0) | NA | 1 (2.8) | 2 (25.0) | NA | 3 (6.5) |
Diarrhea | 2 (7.7) | 0 (0.0) | NA | 0 (0.0) | 2 (25.0) | NA | 2 (4.3) |
Laboratory Parameters | Results | Normal Range | |
---|---|---|---|
Leukocyte count, mean (±SD) | 5824 (±2428) cells/μL | 3600–9600 cells/μL | |
Leukocytes increase, n (%) | 4 (8.7) | ||
Neutrophil count, mean (±SD) | 3840 (±1973) cells/μL | 1400–6500 cells/μL | |
Neutrophils increase, n (%) | 1 (2.2) | ||
Lymphocyte count, median (IQR) | 1265 (855, 1757) cells/μL | 1200–3400 cells/μL | |
Lymphocytes decrease, n (%) | 17 (37.0) | ||
Hemoglobin, mean (±SD) | 13.6 (±1.3) g/dL | 12.1–17.2 g/dL | |
Anemia, n (%) | 2 (4.3) | ||
C-reactive protein, mean (±SD) | 14.1 (±3.8) mg/L | 0–3.00 mg/L | |
Inflammatory syndrome, n (%) | 26 (60.5) | ||
AST, mean (±SD) | 35.5 (±21.5) U/L | 14–36 U/L | |
TGP increase, n (%) | 12 (26.1) | ||
ALT, mean (±SD) | 34.3 (±14.9) U/L | 4–35 U/L | |
TGO increase, n (%) | 11 (23.9) | ||
LDH, median (IQR) | 197 (167, 209) U/L | 120–246 U/L | |
LDH increase, n (%) | 2 (4.3) | ||
CK¸ mean (±SD) | 69.5 (±19.5) U/L | 55–170 U/L | |
CK increase, n (%) | 3 (6.5) | ||
Urea, median (IQR) | 31.5 (20.5, 35.0) mg/dL | 19.26–42.8 mg/dL | |
Urea increase, n (%) | 12 (26.1) | ||
Creatinine, mean (±SD) | 0.6 (±0.2) mg/dL | 0.66–1.25 mg/dL | |
Creatinine increase, n (%) | 3 (6.5) | ||
Glucose, mean (±SD) | 105 (±14) mg/dL | 74–106 mg/dL | |
Glucose increase, n (%) | 16 (34.8) |
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Streinu-Cercel, A.; Miron, V.D.; Oană, A.A.; Irimia, M.; Popescu, R.Ș.; Dărămuș, I.A.; Moțoi, M.M.; Ceapraga, G.J.; Săndulescu, O. Real-World Use of Molnupiravir in the Treatment of Outpatients with SARS-CoV-2 Infection—A Patient Profile Based on the Experience of a Tertiary Infectious Disease Center. Pharmaceuticals 2022, 15, 1065. https://doi.org/10.3390/ph15091065
Streinu-Cercel A, Miron VD, Oană AA, Irimia M, Popescu RȘ, Dărămuș IA, Moțoi MM, Ceapraga GJ, Săndulescu O. Real-World Use of Molnupiravir in the Treatment of Outpatients with SARS-CoV-2 Infection—A Patient Profile Based on the Experience of a Tertiary Infectious Disease Center. Pharmaceuticals. 2022; 15(9):1065. https://doi.org/10.3390/ph15091065
Chicago/Turabian StyleStreinu-Cercel, Anca, Victor Daniel Miron, Alina Alexandra Oană, Mădălina Irimia, Ramona Ștefania Popescu, Ioana Andreea Dărămuș, Maria Magdalena Moțoi, Gabriela Jana Ceapraga, and Oana Săndulescu. 2022. "Real-World Use of Molnupiravir in the Treatment of Outpatients with SARS-CoV-2 Infection—A Patient Profile Based on the Experience of a Tertiary Infectious Disease Center" Pharmaceuticals 15, no. 9: 1065. https://doi.org/10.3390/ph15091065