Molnupiravir for mild to moderate COVID-19

15 minutes to Read
Contributor
He Ako Hiringa, reviewed by Eamon Duffy
20 May 2022
Molnupiravir for mild to moderate COVID-19

This resource provides a summary comparison of molnupiravir with nirmatrelvir/ritonavir.


Place in therapy

Molnupiravir (Lagevrio) is the second oral antiviral medicine approved in New Zealand for the treatment of mild to moderate COVID-19 in adults at increased risk of progressing to severe COVID-19, hospitalisation or death. The first medicine was nirmatrelvir/ritonavir (Paxlovid).1 Molnupiravir should only be used where nirmatrelvir/ritonavir is clinically inappropriate or unavailable, as trial data suggest molnupiravir is much less effective.2,3

Just like nirmatrelvir/ritonavir, treatment with molnupiravir should be initiated within five days of symptom onset and patients should be at least 18 years old.3,4 Pharmac access criteria (see box) are the same as that for nirmatrelvir/ritonavir, and prescriptions need to be endorsed accordingly.2 Both treatments are taken twice daily, and neither is recommended in pregnant patients,3,4 but similarities, for the most part, end there.


Efficacy

Evidence suggests nirmatrelvir/ritonavir is much more effective than molnupiravir. Results from the MOVe-OUT trial in 1433 unvaccinated, at-risk patients with mild to moderate COVID-19 showed early promise after a planned interim analysis, but final analysis showed the relative risk reduction in admissions and deaths was only 30 per cent in the molnupiravir group.3 In contrast, the pivotal nirmatrelvir/ritonavir trial (EPIC-HR) in a similar patient population found an 89 per cent relative reduction in hospital admissions and deaths versus placebo.4

Looking at numbers needed to treat (NNT), the MOVe-OUT trial final analysis suggests that 33 patients would need to be treated with molnupiravir to prevent one admission or death (NNT = 33).5 If you were to apply the 89 per cent reduction from the EPIC-HR trial to the baseline population risk in the MOVe-OUT study, it would show an NNT of around 11 for nirmatrelvir/ritonavir.


Mechanism of action

Molnupiravir is a ribonucleoside prodrug of N-hydroxycytidine (NHC), which has activity against SARS-CoV-2 and other RNA viruses.

Molnupiravir works quite differently from nirmatrelvir/ritonavir: rather than being a SARS-CoV-2 protease inhibitor, molnupiravir is a mutagenic ribonucleoside. Circulating NHC is phosphorylated in cells and incorporated into viral RNA via viral polymerase, which results in viral mutations and lethal mutagenesis. A key challenge for “nucleotide-mimic” drugs is the theoretical risk of metabolism by human host cells and incorporation into host DNA, leading to mutations.6 Based on available data, mutagenicity and genotoxicity risk is considered low in clinical use; however, the following precautions are recommended.3

Because of a lack of human data, neither drug is recommended during pregnancy.3,4 Women of childbearing potential should avoid becoming pregnant during, and for four days after stopping molnupiravir. Men or transwomen with partners of childbearing potential should use reliable contraception during and for at least three months after treatment ends.3 The three-month duration is precautionary to ensure turnover of any potentially affected spermatozoa. Patients should be counselled about these risks and precautions by their prescriber and pharmacist.


Dosage

The recommended molnupiravir dose is 800mg (four 200mg capsules) every 12 hours for five days.3
Patients with renal or hepatic impairment do not need their molnupiravir dose adjusted3, whereas a nirmatrelvir dose reduction is required in patients with moderate renal impairment taking nirmatrelvir/ritonavir.4 Further, nirmatrelvir/ritonavir is not recommended for patients with severe renal or hepatic impairment.4


Interaction potential

Unlike nirmatrelvir/ritonavir, where potential drug interactions may lead to clinically significant adverse reactions,4 neither molnupiravir nor NHC are inhibitors or inducers of major drug-metabolising enzymes or transporters.3 Therefore, it is unlikely molnupiravir or NHC will interact with concomitant medications and, as yet, no drug–drug interactions have been identified.3

Adverse effects commonly occurring with molnupiravir are diarrhoea, nausea and dizziness.3


Molnupiravir access criteria – from any relevant practitioner2

Approvals are valid for patients where the prescribing clinician confirms the patient meets the following criteria, and has endorsed the prescription accordingly:

The patient has confirmed (or probable) symptomatic COVID-19, or has symptoms consistent with COVID-19 and is a household contact of a positive case AND symptoms started within the last five days AND supplemental oxygen is not required.

AND either:

The patient meets ONE of the following:

  • They are immunocompromised and not expected to reliably mount an adequate immune response to COVID-19 vaccination or SARS-CoV-2 infection, regardless of vaccination status; or
  • They have Down syndrome; or
  • They have sickle cell disease; or

The patient has at least FIVE of the following factors:

Molnupiravir is not to be used in conjunction with other COVID-19 antiviral treatments.

Always check the Pharmac website for the most current access criteria and links to Ministry of Health definitions.


Self-audit reflection activity

This activity allows primary care prescribers to self-assess their use of oral antiviral medicines for the treatment of patients with COVID-19. Endorsed by the RNZCGP for up to two CME credits for Continuing Professional Development purposes, the self-audit reflection activity may also be adapted to suit the learning needs of dispensing pharmacists and primary care nurses.

The activity is formatted as an editable PDF, please note that this will not automatically save to your device. You must download the document, save it to your device, and then fill it in.

Click here to complete the self-audit reflection activity.

Professional college endorsements

This activity has been endorsed by The Royal New Zealand College of General Practitioners (RNZCGP) and has been approved for 0.25 CME credits for Continuing Professional Development (CPD) purposes. To claim your credits, log in to your RNZCGP dashboard to record this activity in the CME component of your CPD programme.

This activity has been endorsed by the Pharmaceutical Society of NZ Inc (PSNZ) as suitable for inclusion in a pharmacist’s CE records for Continuing Professional Development (CPD) purposes.

RNZCGP logoPSNZ logo

References

  1. Medsafe. Approval status of COVID-19 treatment applications received by Medsafe. Revised 14 April 2022. www.medsafe.govt.nz/COVID-19/treatment-applications.asp#veklury Accessed May 2022.
  2. Pharmac. Updated Access Criteria for antiviral COVID-19 treatments. 28 April 2022. https://pharmac.govt.nz/news-and-resources/consultations-and-decisions/2022-04-28-decision-oral-covid-treatment-widened-access/ Accessed May 2022.
  3. New Zealand Ministry of Health. Medsafe data sheet (Lagevrio). Last revision 14 April 2022. www.medsafe.govt.nz/Profs/Datasheet/l/lagevirocap.pdf Accessed May 2022.
  4. New Zealand Ministry of Health. Medsafe data sheet (Paxlovid). Last revision 07 April 2022. www.medsafe.govt.nz/profs/Datasheet/p/paxlovidtab.pdf Accessed May 2022.
  5. BC Covid Therapeutics Committee. Clinical Practice Guide for Therapeutics in Patients with Mild-Moderate COVID-19. 12 April 2022. www.bccdc.ca/Health-Professionals-Site/Documents/COVID-treatment/ClinicalPracticeGuide_Therapeutics_MildModerateCOVID.pdf Accessed May 2022.
  6. US National Institutes of Health. COVID-19 treatment guidelines: Molnupiravir. Last updated 24 February 2022. www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/molnupiravir Accessed May 2022.

Content updates

  • 10 June 2022: The statistic relating to reduction in hospitalisation/death was updated from 88 per cent to 89 per cent. (Efficacy section)
  • 10 June 2022: The NNT for nirmatrelvir/ritonavir based on the MOVe-OUT study was updated from 18 to 11. (Efficacy section)