Molvir

Approved Indication:

• Treatment of Mild to Moderate COVID-19 (SARS-CoV-2 infection):
  Molnupiravir is indicated for the treatment of mild to moderate COVID-19 in adults who:
• Have a confirmed positive SARS-CoV-2 test,
• Are within 5 days of symptom onset, and
• Are at high risk for progressing to severe COVID-19, including hospitalization or death.
  This includes individuals with comorbidities such as diabetes, obesity, cardiovascular disease, chronic lung disease, or immunocompromised conditions.

Clinically Accepted Off-Label Use (Under Investigation):

• Post-exposure Prophylaxis (PEP):
  Although not formally approved, Molnupiravir is being evaluated in some trials for preventing symptomatic SARS-CoV-2 infection following confirmed exposure.

Adults (≥18 years):

• Dose: 800 mg orally every 12 hours
• Route: Oral
• Frequency: Twice daily (every 12 hours)
• Duration: For 5 days only
• Maximum Total Duration: Do not exceed 5 days of therapy
• Initiation Window: Start treatment within 5 days of symptom onset

Pediatric Use (<18 years):

• Not recommended. Safety and efficacy have not been established.

Elderly Patients:

• No dosage adjustment required. Use as in adults, but monitor closely due to age-related comorbidities.

Renal Impairment:

• No dosage adjustment is necessary. Molnupiravir is not renally eliminated.

Hepatic Impairment:

• No dosage adjustment is necessary. Hepatic metabolism is minimal.

Administration Instructions:

• Administer with or without food.
• Swallow capsules whole; do not open, crush, or chew.
• Missed dose: If a dose is missed and it's less than 10 hours from the scheduled time, take it as soon as possible. Otherwise, skip the dose and continue with the next scheduled dose.

Molnupiravir is a prodrug of the ribonucleoside analog N-hydroxycytidine (NHC). Once absorbed, it is metabolized into its active form, which is incorporated into the viral RNA by the SARS-CoV-2 RNA-dependent RNA polymerase. This causes viral error catastrophe by introducing excessive mutations (lethal mutagenesis) in the viral genome. As the virus replicates with these faulty RNA strands, its ability to produce viable, infectious progeny is impaired, ultimately reducing viral load and preventing disease progression.

• Absorption: Rapidly absorbed; peak plasma concentrations of NHC occur approximately 1.5 hours after oral dosing.
• Bioavailability: High, especially when taken without food.
• Distribution: Widely distributed; the active metabolite NHC is present in plasma.
• Metabolism: Molnupiravir is rapidly hydrolyzed to NHC by host esterases. NHC is phosphorylated intracellularly to its active triphosphate form.
• Elimination:
• Primary route: Renal elimination of NHC
• Excretion: Minimal unchanged molnupiravir in urine
• Half-life: Approximately 3.3 hours for NHC
• Steady State: Achieved within 2 days of twice-daily dosing
• Food Effect: Food has minimal impact on overall exposure to NHC.

• Pregnancy:
  Molnupiravir is not recommended during pregnancy due to potential fetal harm based on animal studies showing embryo-fetal toxicity. Women of childbearing potential should use effective contraception during treatment and for 4 days after the last dose.
• Lactation:
  It is not known if Molnupiravir or its metabolites are excreted in human milk. Due to potential risks to infants, breastfeeding is not recommended during treatment and for 4 days after the final dose.
• Contraceptive Guidance:
• Women: Use effective contraception during and for 4 days after treatment.
• Men with partners of childbearing potential: Use contraception during and for at least 3 months after treatment due to potential reproductive toxicity.

• Primary Class: Antiviral Agent
• Subclass: Oral RNA Polymerase Inhibitor (Lethal Mutagenesis Agent)
• Antiviral Category: Direct-acting antiviral (DAA) for SARS-CoV-2

• Known hypersensitivity to Molnupiravir or any of its components
• Use in pregnancy unless the potential benefit justifies the risk
• Pediatric use (<18 years) is contraindicated due to potential effects on bone and cartilage growth
• Co-administration with drugs that may alter the metabolism of nucleoside analogs is not recommended without close monitoring

• Embryo-Fetal Toxicity: Avoid use in pregnancy; potential mutagenic and teratogenic effects demonstrated in animal studies.
• Not Authorized for Pre- or Post-Exposure Prophylaxis: Use only in patients with confirmed SARS-CoV-2 infection.
• Mutagenicity Concerns: Although not confirmed in human studies, Molnupiravir induces viral mutagenesis and raises concerns about off-target mutagenic risk.
• Bone and Cartilage Effects (Animal Data): Not recommended in individuals under 18 years due to potential effects on growth.
• Male Fertility: Use of effective contraception advised for men during and 3 months after use.
• Limited Data: Long-term safety and resistance patterns are still under investigation.

Common Adverse Effects (≥1%):

• Gastrointestinal: Diarrhea, nausea, vomiting, abdominal pain
• Nervous System: Headache, dizziness
• General: Fatigue, flu-like symptoms

Less Common/Rare Side Effects:

• Rash, insomnia, increased liver enzymes (transaminases)

Serious Adverse Events:

• None commonly observed in short-term clinical trials
• Long-term genotoxicity or carcinogenicity unknown

Onset and Duration:

• Most adverse effects are mild to moderate in severity and occur within the first 1–3 days of treatment.

• No clinically significant drug-drug interactions have been identified to date.
• Enzyme System Involvement:
• Molnupiravir and its active metabolite (NHC) are not substrates, inducers, or inhibitors of major CYP450 enzymes or transporters (e.g., P-gp, BCRP, OATP).
• Drug-Food Interaction:
• Food does not significantly affect NHC plasma exposure; the drug can be taken with or without food.
• Drug-Alcohol Interaction:
• No specific interactions known, but alcohol should be avoided in patients with COVID-19 due to general immunosuppressive effects.

• FDA Emergency Use Authorization (EUA):
  Molnupiravir received EUA from the FDA in December 2021. It remains under conditional use pending further clinical trial data.
• WHO Guidance (2022–2024):
  WHO conditionally recommends Molnupiravir for non-severe COVID-19 in high-risk patients where other treatments are not available or appropriate.
• EMA Position:
  The EMA has provided conditional approval in some EU countries for early outpatient treatment of COVID-19.
• Ongoing Trials:
  Additional studies are underway evaluating Molnupiravir in different variants, populations, and potential prophylactic use.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Excursion Range: Permissible from 15°C to 30°C (59°F to 86°F)
• Humidity: Store in a dry environment
• Light Protection: Keep in original packaging to protect from light
• Handling Instructions:
• Do not use after the expiration date
• Keep out of reach of children
• No refrigeration required
• Capsules must be stored in their blister pack until use; do not remove in advance