Lagevrio Prescribing Guide

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Lagevrio® (molnupiravir) is a Prescription Medicine and is available as 200 mg capsules.

Please review the Lagevrio Data Sheet before prescribing. The Data Sheet is available at www.medsafe.govt.nz.

INDICATION: Provisional consent for the treatment of mild to moderate coronavirus disease (COVID-19) in adults aged 18 years and older who are at increased risk of progressing to severe COVID-19, hospitalisation or death.

CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the excipients.

PRECAUTIONS: Use in pregnancy is not recommended; consider the need for a pregnancy test before initiating treatment in women of childbearing potential who are sexually active.

It is recommended that sexually active women of childbearing potential use contraception during and for 4 days after the last dose, and that men who are sexually active with a partner of childbearing potential use an adequate form of contraception during and for 3 months after treatment. Breastfeeding is not recommended during treatment and for 4 days after the last dose. Safety and efficacy of Lagevrio have not been established in patients < 18 years, therefore use in paediatric patients is not recommended. Hypersensitivity reactions have been reported; if signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue Lagevrio and initiate appropriate medications and/or supportive care.

INTERACTIONS: No drug interactions have been identified based on the limited available data. Potential for interaction with concomitant medications is considered unlikely.

ADVERSE EVENTS: Common: diarrhoea, nausea, dizziness. The following have been reported in post-marketing experience: hypersensitivity, angioedema, erythema, rash, urticaria.

DOSAGE AND ADMINISTRATION: Adults: 800 mg (four 200 mg capsules) taken orally every 12 hours for 5 days, with or without food. Safety and efficacy when administered for periods longer than 5 days have not been established. Lagevrio should be administered as soon as possible after a diagnosis of COVID-19 has been made and within 5 days of symptom onset.

Based on Data Sheet dated 14 April 2022.

Lagevrio is funded if the patient meets the Access Criteria for oral antiviral COVID-19 treatment (as per Pharmac’s website) and the prescriber has endorsed the prescription.

The supply of treatment is via Pharmac’s approved distribution process.1 Merck Sharp & Dohme (New Zealand) Limited. Level 3, 123 Carlton Gore Road, Newmarket, Auckland.

NZ-LAG-00030. First issued May 2022. TAPS DA 2208KN. INSIGHT 11475.

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Prescribing Guide LAGEVRIO® (molnupiravir) has provisional consent for the treatment of mild to moderate coronavirus disease (COVID-19) in adults aged 18 years and older who are at increased risk of progressing to severe COVID-19, hospitalisation or death.2

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Important prescribing information OUTPATIENT STUDY

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Must be taken within five days of developing symptoms.2 OLDER AGE

Recommended dose: 800 mg (four 200 mg capsules) taken orally every 12 hours, for five days. Patients may take capsules with or without food.2 INDIVIDUAL No drug interactions (based on limited available data): NHC (n-hydroxycytidine), the metabolised form of Lagevrio, MASK is not a substrate of major drug metabolising enzymes or transporters. Neither Lagevrio nor NHC are inhibitors or inducers of major drug metabolising enzymes or transporters.2

HOSPITALIZED PATIENT STUDY

RESPIRATORY SYSTEM

DOSING

Pregnancy, Breastfeeding and Contraception: ALT OLDER

HYPERTENSION

RACE

AGE Lagevrio is not recommended during pregnancy or breastfeeding.

Consider the need for a pregnancy test before initiating treatment in women of childbearing potential are sexually active.

It is ALT TEST AT TEST AT ALTwho INDIVIDUAL PRIMARY CARE recommended that sexually PRIMARY activeCARE women of childbearing potential use contraception during and for 4 days after the last dose, and that men who are sexually active PROJECTION UPWARD with a partner of childbearing FOOD TREND potential use an adequate form of contraception during and for 3 months after treatment.

Breastfeeding is not recommended during treatment and for 4 days after the last dose.2

No dose adjustments: - for elderly patients - for patients with renal impairment - for patients with hepatic impairment 2

*Capsules not actual size

SYM IMP

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Clinical Trial Results

RISK REDUCTION OF HOSPITALISATION AND/OR DEATH2

Lagevrio was evaluated in the MOVe-OUT trial: A phase 3, randomised, double blind, placebo-controlled clinical trial evaluating its efficacy and safety in non-hospitalised adults with mild to moderate COVID-19 who were at risk of progressing to severe COVID-19 and/or hospitalisation. Study design is detailed on page 6.

Primary endpoint: percentage of patients who were hospitalised or died through day 29 due to any cause.

EFFICACY RESULTS IN NON-HOSPITALISED ADULTS WITH COVID-192 Interim Analysis

Lagevrio (N=385) n (%)

Placebo (N=377) n (%)

All-cause hospitalisation or death through Day 29

28 (7.3%)

53 (14.1%)

Hospitalisation‡

28 (7.3%)

52 (13.8%)

Death

0 (0%)

8 (2.1%)

Unknown§

0 (0%)

1 (0.3%)

Risk Difference* (95% CI) -6.8% (-11.3%, -2.4%)

p-Value† 0.0012

All-Randomised Analysis^ Lagevrio (N=709) n (%)

Placebo (N=699) n (%)

All-cause hospitalisation or death through Day 29

48 (6.8%)

68 (9.7%)

Hospitalisation‡

48 (6.8%)

67 (9.6%)

Death

1 (0.1%)

9 (1.3%)

0 (0%)

1 (0.1%)

Unknown

§

* Risk difference of molnupiravir-placebo based on Miettinen and Nurminen method stratified by time of COVID-19 symptom onset (≤3 days vs. >3 [4-5] days). † 1-sided p-Value ‡ Defined as ≥24 hours of acute care in a hospital or an acute care facility (e.g., emergency room). § Subjects with unknown status at Day 29 are counted as having an outcome of all-cause hospitalisation or death in the efficacy analysis.

Note: All subjects who died through Day 29 were hospitalised prior to death.

Risk Difference* % (95% CI) -3.0% (-5.9%, -0.1%)

^ Because the efficacy results at the interim analysis met the statistical criterion for superiority over placebo, no additional formal statistical testing was planned for the primary efficacy end point.2 For interim analysis subjects: Relative risk reduction of molnupiravir compared to placebo is 48% (95% CI: 20%, 67%) based on the Cochran-Mantel-Haenszel method stratified by time of COVID-19 symptom onset (≤3 days vs. >3 [4-5] days) For all randomized subjects: Relative risk reduction of molnupiravir compared to placebo is 30% (95% CI: 1%, 51%) based on the Cochran-Mantel-Haenszel method stratified by time of COVID-19 symptom onset (≤3 days vs. >3 [4-5] days)

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Adverse Reactions & Contraindications2 ADVERSE REACTIONS OCCURRING IN GREATER THAN OR EQUAL TO 1% OF SUBJECTS RECEIVING LAGEVRIO IN MOVe-OUT2*

Lagevrio % N=710

Placebo % N=701

Diarrhoea

2%

2%

Nausea

1%

1%

Dizziness

1%

1%

*Frequencies of adverse reactions are based on all adverse events attributed to study intervention by the investigator.

Serious adverse events occurred in 7% of subjects receiving Lagevrio and 10% receiving placebo; most serious adverse events were COVID-19 related.2 Adverse events leading to death occurred in <1% of the subjects receiving Lagevrio and 1.7% of the subjects receiving placebo.2 The following adverse reactions have been identified during post-marketing use of Lagevrio: hypersensitivity, angioedema, erythema, rash, urticaria.2 CONTRAINDICATIONS2

Hypersensitivity to the active substance or any of the excipients.2

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Access Criteria & Information on Risk Factors for Severe COVID-19

OLDER AGE

INDIVIDUAL

Lagevrio is funded if the patient meets the Access Criteria for oral antiviral COVID-19 treatment (as per Pharmac’s website) and the prescriber has endorsed the prescription.1 The Access Criteria is MASK available at: https://pharmac.govt.nz/news-and-resources/covid19/ covid-oral-antivirals/

Information for people at risk of severe COVID-19 can be found on the Ministry of Health website, available at: https://www.health.govt.nz/covid-19-novel-coronavirus/ covid-19-information-specific-audiences/covid-19-higher-risk-people

Study Design The MOVe-OUT trial was a phase 3, randomised, placebo-controlled, double-blind clinical trial studying Lagevrio for the treatment of non-hospitalised patients with mild to moderate COVID-19 who were at risk of progressing to severe COVID-19 and/ or hospitalisation. Eligible patients were 18 years of age and older and had one or more pre-defined risk factors for disease progression: over 60 years of age, diabetes, obesity (BMI ≥30), chronic kidney disease, serious heart conditions, chronic obstructive pulmonary disease, or active cancer. The study included symptomatic patients not vaccinated against SARS-CoV-2 and who had laboratory confirmed SARS-CoV-2 infection and symptom onset within 5 days of randomisation. A total of 1433 patients were randomised 1:1 to receive 800 mg of Lagevrio or placebo orally twice daily for 5 days. The primary endpoint was the percentage of patients who were hospitalised or died through Day 29 due to any cause.2

References: 1. Pharmac. Pharmaceutical Schedule. Available at: https://schedule.pharmac. govt.nz/ScheduleOnline.php. Accessed on: 26 Apr 2022. 2. Lagevrio Data Sheet. 3. Bernal AJ et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med 2022;386:509-20.

Copyright © 2022 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved.

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