CYMOVIR-200

Mechanism of Action

Molnupiravir is a prodrug with antiviral activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Molnupiravir is hydrolyzed during or after absorption to form the cytidine nucleoside analog, N4-hydroxycytidine (NHC), which distributes into cells. Once inside the cells, NHC is phosphorylated to form the active ribonucleoside triphosphate (NHC-TP). Viral RNA polymerase (nsp12) then incorporates NHC-TP (as NHC-monophosphate [NHC-MP]) into SARS-CoV-2 RNA. This causes an accumulation of errors in the viral genome leading to inhibition of viral replication (i.e., viral error catastrophe or viral lethal mutagenesis).

PharmacoKinetics

Molnupiravir is administered orally. During or after absorption, molnupiravir is hydrolyzed to the cytidine nucleoside analog, N4-hydroxycytidine (NHC). NHC is the primary circulating component, with an apparent volume of distribution of 142 L. NHC is not bound to plasma proteins, but rather enters into cells were it is phosphorylated to form the pharmacologically active ribonucleoside triphosphate (NHC-TP). NHC is eliminated by metabolism to uridine and cytidine through the same pathways involved in endogenous pyrimidine metabolism. NHC has an apparent clearance of 76.9 L/hour and an effective half-life of approximately 3.3 hours. The fraction of dose excreted as NHC in the urine is up to 3%.[67209]

Absorption

After an 800 mg oral dose of molnupiravir every 12 hours, the active compound (N4-hydroxycytidine) reaches a Cmax of 2970 ng/mL, with a Tmax of 1.5 hours, and an AUC0-12h of 8360 h*ng/mL.

Protein binding

Molnupiravir and the active metabolite, N4-hydroxycytidine, are not protein bound in plasma.

Metabolism

Molnupiravir is hydrolyzed to N4-hydroxycytidine, which distributes into tissues. Once inside cells, N4-hydroxycytidine is phosphorylated to the 5′-triphosphate form.

Route of elimination 

-≤3% of an oral molnupiravir dose is eliminated in the urine as the active metabolite N4-hydroxycytidine

Adverse Reactions

Mild- Diarrhea, Dizziness, Nausea, Rash, Urticaria.
Severe- Anaphylactoid reactions, Angioedema.
Moderate- Erythema.

Indications

1. It is used by adults 18 years of age and older who have recently tested positive for coronavirus
2. Molnupiravir may help people who have recently tested positive for coronavirus stay out of the hospital.

Warnings and Precautions

1. Before taking this medication, tell your doctor if you have any allergies. This product may contain inactive ingredients which can cause allergic reactions or other problems.

2. Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while taking molnupiravir. Molnupiravir may harm an unborn baby. Your doctor may do a pregnancy test before you start taking this medication.

3. It is unknown if molnupiravir passes into breast milk. Because of the possible risk to the infant, breast-feeding is not recommended while using this drug and for 4 days after stopping the drug. Ask your doctor if you should pump and discard your breast milk during treatment and for 4 days after the last dose of this drug.

Drug Interactions

Drug interactions Information is limited, and it is unknown at this time if molnupiravir has drug interactions.

Storage

Do not store above 30°C.
Store in the original package in order to protect from moisture.
Keep all medications away from children and pets.

Overdose

Patients who ingest more than the recommended dosage should be closely monitored for myelosuppression and given appropriate supportive treatment.

Contraindications

• Antimicrobial resistance
• Breast-feeding
• Contraception requirements
• Reproductive risk