Lagevrio 200 mg Capsules

LAGEVRIO TM (molnupiravir) capsules are indicated for treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults with a positive SARS-COV-2 diagnostic test, who do not require supplemental oxygen due to COVID-19 and who have at least one risk factor for developing severe illness [see section 5.1 Clinical Studies].

Posology

Adults

The recommended dose of LAGEVRIO TM in adult patients is 800 mg (four 200 mg capsules) taken orally every 12 hours for 5 days, with or without food. Should a patient require hospitalization after starting treatment with LAGEVRIO TM, the patient may complete the full 5 day treatment course per the healthcare provideru2019s discretion.

The safety and efficacy of LAGEVRIO TM when administered for periods longer than 5 days have not been established. LAGEVRIO TM 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 hospitalization or death. Certain medical conditions or other factors may place individual patients at increased risk for progression to severe COVID-19 [see section 5.1 Clinical Studies].

Missed dose

If the patient misses a dose of LAGEVRIO TM 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.

Special populations

Elderly Use

No dose adjustment of LAGEVRIO TM is recommended for elderly patients [see section 5.2 Gender, Race and Age].

Renal Impairment

The pharmacokinetics of molnupiravir and NHC has not been evaluated in patients with eGFR less than 30 mL/min or on dialysis.

Hepatic Impairment

No dose adjustment of LAGEVRIO TM is recommended in patients with hepatic impairment [see section 5.2 Hepatic Impairment].

Paediatric use

Safety and efficacy of LAGEVRIO TM have not been established in patients less than 18 years of age [see section s 5.2 Paediatric Population and 5.3 General Toxicity].

Pregnancy

Hypersensitivity to the active ingredient, molnupiravir or to any excipients of LAGEVRIO TM listed in section 6.1

None

No drug interactions have been identified based on the limited available data. Clinical drug-drug interaction trials of LAGEVRIO TM with concomitant medications have not been conducted. Molnupiravir is hydrolyzed 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 molnupiravir nor NHC are inhibitors or inducers of major drug metabolizing enzymes or transporters. Therefore, the potential for molnupiravir or NHC to interact with concomitant medications is considered unlikely.

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 TM (molnupiravir).

Risk Summary

Based on animal data, LAGEVRIO TM may cause foetal harm when administered to pregnant women. There are no available data on the use of LAGEVRIO TM in pregnant women to evaluate the risk of major birth defects, miscarriage or adverse maternal or foetal outcomes. The use of LAGEVRIO TM is not recommended during pregnancy. In an animal reproduction study, oral administration of molnupiravir to pregnant rats during the period of organogenesis resulted in embryofoetal lethality and teratogenicity at 8 times the human NHC exposures at the recommended human dose (RHD) and reduced foetal growth at u2265 3 times the human NHC exposure at the RHD. Oral administration of molnupiravir to rabbits during the period of organogenesis resulted in reduced foetal body weights at 18 times the human NHC exposure at the RHD [see section 5.3 Development].

Breastfeeding

It is unknown whether molnupiravir or any of the components of molnupiravir are present in human milk, affect human milk production, or have effect on the breastfed infant. NHC was detected in the plasma of nursing pups from lactating rats administered molnupiravir. Based on the potential for adverse reactions on the infant from LAGEVRIO TM, breastfeeding is not recommended during treatment and for 4 days after the last dose of LAGEVRIO TM.

Fertility

There were no effects on female or male fertility in rats at NHC exposures approximately 2 and 6 times respectively, the exposure in humans at the recommended human dose (RHD).

LAGEVRIO TM has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most common adverse reactions in patients treated with 800 mg molnupiravir every 12 hours for 5 days in the Phase 3 MOVe-OUT clinical trial were diarrhoea (2 %), nausea (1 %), and dizziness (1 %), all of which were Grade 1 (mild) or Grade 2 (moderate) in severity.

Tabulated summary of adverse reactions

The adverse reactions are listed below by MedDRA system organ class and frequency. Frequencies are defined as follows: Very common (u2265 1/10); common (u2265 1/100 to < 1/10); uncommon (u2265 1/1,000 to < 1/100); rare (u2265 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

Table 1: Tabulated summary of adverse reactions

Frequency Adverse Reaction Immune System Disorders Uncommon hypersensitivity Nervous system disorders Common dizziness, headache Gastrointestinal disorders Common diarrhoea, nausea Uncommon vomiting Skin and subcutaneous tissue disorders Uncommon angioedema, erythema, rash, urticaria

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

There is no human experience of overdosage with LAGEVRIO TM. Treatment of overdose with LAGEVRIO TM 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.