LAGEVRIO®

LAGEVRIO^® (molnupiravir) SELECTED SAFETY INFORMATION

Based on approved PI dated 22 April 2022

Warnings and Precautions

Use in Pregnancy (Category D) and Lactation

LAGEVRIO is not recommended during pregnancy. Advise women of childbearing potential to use effective contraception for the duration of treatment and for 4 days after the last dose of LAGEVRIO. Based on animal data, LAGEVRIO may cause foetal harm when administered to pregnant women. There are no available data on the use of LAGEVRIO in pregnant women to evaluate the risk of major birth defects, miscarriage or adverse maternal or foetal outcomes.

It is unknown whether LAGEVRIO or any of the components of LAGEVRIO are present in

human milk, affect human milk production, or have effect on the breastfed infant. Based on the potential for adverse reactions on the infant from LAGEVRIO, breastfeeding is not recommended during treatment and for 4 days after the last dose of LAGEVRIO.

Contraception

There is no data available in relation to whether LAGEVRIO affects sperm. It is recommended that men who are sexually active with a partner of childbearing potential use an adequate form of contraception during and 3 months after treatment with LAGEVRIO.

It is recommended that sexually active women of childbearing potential use contraception during, and for 4 days after treatment with LAGEVRIO.

Paediatric Use

Safety and efficacy of LAGEVRIO have not been established in patients less than 18 years of age. LAGEVRIO is not recommended for paediatric use.

Hypersensitivity

Hypersensitivity reactions have been reported with LAGEVRIO. If signs or symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue LAGEVRIO and initiate appropriate medications and/or supportive care.

Effects on ability to Drive and use Machines

LAGEVRIO is predicted to have no or negligible influence on the ability to drive and use machines.

Adverse Reactions

The most common adverse reactions occurring in ≥1 % of subjects in the LAGEVRIO treatment group in the Phase 3 double-blind MOVe-OUT study were diarrhoea (2% versus placebo at 2%), nausea (1% versus placebo at 1%), and dizziness (1% versus placebo at 1%) all of which were Grade 1 (mild) or Grade 2 (moderate). Serious adverse events occurred in 7 % of subjects receiving LAGEVRIO and 10 % receiving placebo; most serious adverse events were COVID-19 related. Adverse events leading to death occurred in <1 % of the subjects receiving LAGEVRIO and 2 % of subjects receiving placebo.

Post Marketing Experience

The following adverse reactions have been identified during post-marketing use of LAGEVRIO: hypersensitivity, angioedema, erythema, rash and urticaria.

Drug Interactions

No drug interactions have been identified based on the limited available data.

LAGEVRIO is hydrolysed to n-hydroxycytidine (NHC) prior to reaching systemic circulation. Uptake

and metabolism of NHC are mediated by the same pathways involved in endogenous pyrimidine metabolism. NHC is not a substrate of major drug metabolizing enzymes or transporters. Neither LAGEVRIO nor NHC are inhibitors or inducers of major drug metabolising enzymes or transporters. Therefore, the potential for LAGEVRIO or NHC to interact with concomitant medications is considered unlikely

Dosage and Administration

The recommended dose of LAGEVRIO in adult patients is 800 mg (four 200 mg capsules) taken orally every 12 hours for 5 days, with or without food.

The safety and efficacy of LAGEVRIO 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 in adults who are at risk for progression to severe COVID-19, including hospitalisation or death. Certain medical conditions or other factors may place individual patients at increased risk for progression to severe COVID-19.

In women of childbearing potential, health care providers should discuss the chance that they may be pregnant and consider the need for a pregnancy test.

Missed Dose

If the patient misses a dose of LAGEVRIO within 10 hours of the time it is usually taken, the patient should take it as soon as possible and resume the normal dosing schedule. If a patient misses a dose by more than 10 hours, the patient should not take the missed dose and instead take the next dose at the regularly scheduled time. The patient should not double the dose to make up for a missed dose.

Elderly Patients

No dose adjustment of LAGEVRIO is recommended in geriatric patients. In the MOVe-OUT study there was no difference in the safety and tolerability between patients >65 years of age and younger who were treated with LAGEVRIO

Renal Impairment

No dose adjustment of LAGEVRIO is required in patients with renal impairment.

Hepatic Impairment

No dose adjustment of LAGEVRIO is recommended in patients with hepatic impairment.

Overdose

There is no human experience of overdosage with LAGEVRIO. Treatment of overdose with LAGEVRIO should consist of general supportive measures including the monitoring of the clinical status of the patient. Haemodialysis is not expected to result in effective elimination of NHC.

For information on the management of overdose, contact the Poison Information Centre on 131126.

Indication

LAGEVRIO (molnupiravir) has provisional approvalfor the treatment of adults with COVID-19 who do not require initiation of oxygen due to COVID-19 and who are at increased risk for hospitalisation or death. The decision to approve this indication was based on efficacy and safety data from a Phase 3 trial. Continued approval of this indication depends on additional data.

Contraindications

Hypersensitivity to the active substance or to any of the excipients in LAGEVRIO capsules.