Molnupiravir (Capsules) Instructions for Use

ATC Code

J05AB18 (Molnupiravir)

Active Substance

Molnupiravir (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antiviral drug active against SARS-CoV-2 virus

Pharmacotherapeutic Group

Systemic antiviral agents; direct-acting antiviral agents; nucleosides and nucleotides, excluding reverse transcriptase inhibitors

Pharmacological Action

Molnupiravir is an antiviral agent that is a prodrug metabolized to the ribonucleoside analogue N-hydroxycytidine (NHC). NHC is distributed into cells and phosphorylated to form the pharmacologically active ribonucleoside triphosphate (NHC-TP).

NHC-TP acts via a mechanism known as viral error catastrophe during the virus replication process. The incorporation of NHC-TP into viral RNA by the RNA polymerase enzyme leads to an accumulation of errors in the viral genome, resulting in the suppression of replication.

Molnupiravir helps prevent the risks of complicated COVID-19, including in patients with risk factors for progression to severe disease. Therapy with molnupiravir leads to a reduction in the time to virus elimination and a decrease in the duration of disease symptoms.

Pharmacokinetics

Molnupiravir is a prodrug of 5′-isobutyrate that is hydrolyzed to NHC before entering the systemic circulation. The pharmacokinetics of NHC are similar in healthy individuals and patients with COVID-19.

Steady-state pharmacokinetics of NHC after administration of 800 mg molnupiravir every 12 hours: C_max is 2970 (%CV 16.8) ng/mL, C_{12 h} is 31.1 (%CV 124) ng/mL, AUC _{0-12 h} is 8260 (%CV 41.0) ng×h/mL.

After twice-daily oral administration of 800 mg molnupiravir, the T_max of NHC averages 1.5 hours.

The NHC metabolite does not bind to plasma proteins.

The T_1/2 of NHC is approximately 3.3 hours. The fraction of the dose excreted as NHC in urine was ≤3% in healthy volunteers.

Indications

Treatment of mild to moderate COVID-19 in adults, including those at increased risk of progression to severe disease and not requiring supplemental oxygen.

ICD codes

Dosage Regimen

Take molnupiravir orally as 800 mg twice daily for 5 days.

Administer the total daily dose of 1600 mg as four 200 mg capsules taken twice daily.

Swallow the capsules whole with a sufficient amount of water.

Initiate treatment as soon as possible after a positive COVID-19 diagnosis and within 5 days of symptom onset.

Maintain a consistent dosing schedule, approximately every 12 hours.

If a dose is missed and it is less than 10 hours until the next scheduled dose, skip the missed dose.

If it is more than 10 hours until the next dose, take the missed capsule(s) immediately and resume the normal schedule.

Do not take a double dose to make up for a missed one.

Complete the full 5-day course of treatment even if you start to feel better.

This regimen is indicated for adults with mild to moderate COVID-19 who do not require supplemental oxygen.

Adverse Reactions

Nervous system disorders: common – dizziness, headache.

Gastrointestinal disorders: common – diarrhea, nausea; uncommon – vomiting.

Skin and subcutaneous tissue disorders: uncommon – rash, urticaria.

Contraindications

Hypersensitivity to molnupiravir; pregnancy or planning pregnancy, breastfeeding period; children under 18 years of age.

With caution

In patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m²) and in patients with impaired liver function, monitoring of blood biochemical parameters is necessary.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Dosage adjustment in patients with hepatic impairment is not required.

Use in Renal Impairment

Dosage adjustment in patients with renal impairment is not required.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Dosage adjustment is not required.

Special Precautions

A number of comorbidities increase the risk of progression of COVID-19 to severe disease: age ≥ 60 years, obesity (BMI > 30 kg/m²), diabetes mellitus, chronic kidney disease, severe cardiovascular diseases, chronic obstructive pulmonary disease, active malignancies.

Use of molnupiravir is only possible under medical supervision.

If use in women of reproductive age (including postmenopausal women for less than 2 years) is necessary, a negative pregnancy test result must be confirmed before starting treatment. A repeat pregnancy test should be performed after the end of administration.

Women of childbearing potential should use effective methods of contraception during treatment and for 4 days after its completion. In case of suspected pregnancy, molnupiravir should be discontinued immediately.

Since reproductive toxicity of molnupiravir has been shown in animal studies, the use of effective contraception is recommended in men during molnupiravir administration and for 3 months after its completion.

Effect on ability to drive vehicles and operate machinery

During treatment, refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.