两种新冠口服药对比：Molnupiravir VS Paxlovid

The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) to two oral antiviral therapies for COVID-19. Let’s take a brief look at these two drugs: molnupiravir and Paxlovid. These two treatments have not yet been approved by the FDA, and their known and possible risks and benefits need to be carefully studied before starting treatment.

Molnupiravir (Lagevrio, Monupiravir)

Company: Merck (known as Merck in the United States and Canada)

Generic name and formula: Molnupiravir 200mg; capsule

Pharmacological category: Nucleoside analogues inhibit SARS-CoV-2 replication by inducing viral mutations.

Indications: For the treatment of adult patients with mild to moderate COVID-19 who test positive by direct SARS-CoV-2 viral testing and are at high risk for developing severe COVID-19, including hospitalization or death, and for patients for whom other FDA-authorized COVID-19 treatment options are unavailable or inappropriate. Before starting treatment, carefully consider the known and possible risks and benefits.

Scope of use: Molnupiravir's authorization does not include: patients younger than 18 years of age; patients requiring hospitalization due to COVID-19; patients with more than 5 consecutive days of use; pre-exposure or post-exposure prophylaxis of COVID-19.

DOSAGE: Take immediately after diagnosis of COVID-19 and within 5 days of onset of symptoms. Swallow capsules whole, 800 mg (four 200 mg capsules) orally every 12 hours for 5 days. Can be taken with or without food. Safety and effectiveness in pediatric patients have not been established.

Contraindications: Available data are limited and no contraindications have been identified.

Precautions: It is embryotoxic and is not recommended for use during pregnancy. Individuals of reproductive potential should use effective contraception during treatment and for 4 days after the last dose. Nursing Women: Breastfeeding is not recommended during treatment and for 4 days after the last dose. May affect bone and cartilage growth.

Drug Interactions: Available data are limited and have not been identified.

Adverse reactions: Most common: diarrhea, nausea and dizziness.

Packaging: Each capsule contains 200mg, 40 capsules per bottle.

Paxlovid

Company: Pfizer

Generic name and formula: Nirmatrelvir 150mg; ritonavir 100mg; tablets

Pharmacological category: SARS-CoV-2 main protease inhibitor + HIV-1 protease inhibitor and CYP3A inhibitor.

Indications: For the treatment of adult patients with mild to moderate COVID-19 and pediatric patients 12 years and older weighing at least 40 kg who have tested positive on a direct SARS-CoV-2 viral test and are at high risk of progression to severe COVID-19, including hospitalization or death.

Scope of use: Paxlovid's authorization does not include: patients requiring hospitalization due to severe or critical COVID-19; pre-exposure or post-exposure prophylaxis of COVID-19; patients with more than 5 consecutive days of use.

DOSAGE: Take immediately after diagnosis of COVID-19 and within 5 days of onset of symptoms. Prescriptions should specify the numerical dosage of each active ingredient in Paxlovid. Swallow tablet whole. Take 300 mg nirmatrelvir (two 150 mg tablets) plus 100 mg ritonavir (one 100 mg tablet) each time, 3 tablets taken together, twice a day for 5 consecutive days. Can be taken with or without food.

Contraindications: Concomitant use with drugs that are highly dependent on CYP3A clearance and, if not cleared, can increase concentrations and cause serious and/or life-threatening reactions. Concomitant use with strong CYP3A inducers is contraindicated as it will significantly reduce the plasma concentrations of nirmatrelvir or ritonavir, potentially resulting in loss of virological response and emergence of drug resistance.

Precautions: Ritonavir has been associated with elevated hepatic transaminases, clinical hepatitis, and jaundice. In patients with uncontrolled or undiagnosed HIV-1 infection, there is a risk that HIV-1 may develop resistance to HIV protease inhibitors.

Drug Interactions: See Contraindications. Drugs that induce CYP3A may reduce the plasma concentrations of nirmatrelvir and ritonavir, thereby reducing the therapeutic efficacy of Paxlovid. Paxlovid can alter the plasma concentrations of other drugs. Before and during treatment with Paxlovid, consider potential drug interactions and review concomitant medications during treatment.

Adverse reactions: Most common: dysgeusia, diarrhea, hypertension and myalgia.

Packaging: Blister card, 5 daily dose blister cards, 30 tablets in total. Each blister card contains 4 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each). Morning and evening doses are labeled on the blister card.

Molnupiravir Clinical Trial Introduction

On November 4, 2021, the UK Medicines and Healthcare products Regulatory Agency (MHRA) authorized Molnupiravir (MK-4482, EIDD-2801) for the treatment of adult patients with mild to moderate COVID-19 who test positive for SARS-CoV-2 and have at least one risk factor for developing severe disease.

On December 24, 2021, the Japanese Ministry of Health, Labor and Welfare granted emergency approval to molnupiravir to treat infectious diseases caused by the new coronavirus (SARS-CoV-2).

On December 23, 2021, the US FDA granted emergency use authorization to Molnupiravir.

In the United States, the EUA for molnupiravir is based on data from the Phase 3 MOVe-OUT trial, which compared the efficacy and safety of molnupiravir to placebo in adult non-hospitalized patients within 5 days of symptom onset. The results showed that 29 days after randomization, 6.8% (n=48/709) of patients in the molnupiravir group were hospitalized or died, compared with 9.7% (n=68/699) of patients in the placebo group (absolute risk reduction 3.0%, 95% CI, 0.1-5.9; P =.0218), and a relative risk reduction of 30% (relative risk, 0.70; 95% CI, 0.49-0.99). One death was reported in the Molnupiravir group and nine in the placebo group.

Paxlovid Clinical Trial Introduction

On December 22, 2021, the US FDA granted PAXLOVID emergency use authorization for the treatment of COVID-19. This is the first oral drug for COVID-19 to obtain FDA EUA.

This randomized, double-blind, two-arm, EPIC-HR trial included 2246 patients with laboratory-confirmed SARS-CoV-2 infection and mild to moderate symptoms. Final results showed that Paxlovid significantly reduced the risk of COVID-19-related hospitalization or death from any cause by 88% compared with placebo (P<.0001). On Day 28, 0.8% (8/1039) of patients in the Paxlovid group were hospitalized or died, compared with 6.3% (66/1046) in the placebo group.

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