Molnarz 200 mg Capsule

MOLNARZ is indicated for treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults with a positive SARS-COV-2 diagnostic test and who do not require supplemental oxygen due to COVID - 19 and who have at least one risk factor for developing severe illness (see 5.1 for clinical studies).

Posology
Adults
The recommended dose of MOLNARZ 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 MOLNARZ, the patient may complete the full 5 day treatment course per the healthcare provideru2019s discretion. The safety and efficacy of MOLNARZ when administered for periods longer than 5 days have not been established. MOLNARZ 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 MOLNARZ within 10 hours of the time it is usually taken, the patient should take 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
No dose adjustment of MOLNARZ 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 MOLNARZ is recommended for patients with hepatic impairment (see section 5.2 Hepatic Impairment).
Paediatric population
The safety and efficacy of MOLNARZ in patients below 18 years of age have not been established. No data are available (see sections 5.2 Paediatric Population and 5.3 General Toxicity).
Pregnancy
Based on animal data, MOLNARZ may cause foetal harm. Human pregnancy data are not available. The use of MOLNARZ is not recommended during pregnancy (see section 5.3 Development).
Method of administration
For oral use. MOLNARZ can be taken with or without food. The capsules should be swallowed whole with a sufficient amount of fluid (e.g., a glass of water). The capsules should not be opened, crushed or chewed.

MOLNARZ is contraindicated in patients who have a known history of hypersensitivity to the active substance or any of the other ingredients (see Section 6.1).

Sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per dose of 4 capsules, that is to say essentially u2018sodium-freeu2019.

No interactions have been identified based on the limited available data. No clinical interaction studies have been performed with molnupiravir. Molnupiravir is hydrolysed to n-hydroxycytidine (NHC) prior to reaching systemic circulation. Uptake of NHC and metabolism to NHC-TP are mediated by the same pathways involved in endogenous pyrimidine metabolism. NHC is not a substrate of major medicine metabolising enzymes or transporters. Based on in vitro studies, neither molnupiravir nor NHC are inhibitors or inducers of major medicine metabolising enzymes or inhibitors of major medicine transporters. Therefore, the potential for molnupiravir or NHC to interact with concomitant medications is considered unlikely.

Women of childbearing potential
Advise women of childbearing potential to use effective contraception for the duration of treatment and for 4 days after the last dose of MOLNARZ.
Pregnancy
Risk Summary
Based on animal data, MOLNARZ may cause foetal harm when administered to pregnant women. There are no available data on the use of MOLNARZ in pregnant women to evaluate the risk of major birth defects, miscarriage or adverse maternal or foetal outcomes. The use of MOLNARZ 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]. In a pre- and post-natal developmental study, molnupiravir was administered orally to female rats at doses up to 500 mg/kg/day (1.6 times the human NHC exposure at the RHD) from GD6 through lactation day 20. No effects were observed in offspring.
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. Animal lactation studies with molnupiravir have not been conducted was detected in the plasma of nursing pups from lactating rats administered molnupiravir. Based on the potential for adverse reactions on the infant from MOLNARZ, breastfeeding is not recommended during treatment and for 4 days after the last dose of MOLNARZ.
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).

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

a) Summary of 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: Frequent = very common and common; Less frequent = rare and very rare; not known (cannot be estimated from the available data).
Table 1: Tabulated summary of adverse reactions

There is no human experience of overdosage with MOLNARZ. Treatment of overdose with MOLNARZ 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.