Oral antiviral medications became an important tool in managing COVID-19. Among the first to be authorized were Molnupiravir and Paxlovid, both developed to treat mild to moderate illness in people at high risk for severe disease. These treatments are designed to prevent the progression to more serious outcomes like hospitalization or death.
How Each Drug Fights the Virus
The two medications combat the SARS-CoV-2 virus through different methods. Paxlovid functions as a protease inhibitor. The virus relies on an enzyme called a protease to chop up large proteins into smaller, functional pieces needed to build new virus particles. Paxlovid blocks this enzyme, halting the production of new, infectious copies.
Molnupiravir works by disrupting the virus’s genetic code. It is a nucleoside analog, meaning it mimics one of the building blocks of RNA, the virus’s genetic material. During replication, the virus mistakenly incorporates molnupiravir into its new RNA strands. This introduces widespread errors into the genetic blueprint, a process called viral mutagenesis, resulting in faulty and non-viable virus copies.
Comparing Treatment Effectiveness
The clinical trial for Paxlovid, the EPIC-HR study, showed a reduction in the risk of hospitalization or death. In high-risk, unvaccinated individuals treated within five days of symptom onset, Paxlovid reduced this risk by 89%. This high level of effectiveness established it as a first-line treatment option in many clinical guidelines.
The trial for molnupiravir, the MOVe-OUT study, also demonstrated a benefit, though to a lesser degree. In its study population of high-risk, unvaccinated adults, treatment with molnupiravir reduced the risk of hospitalization or death by 30% compared to a placebo. This difference in initial trial results is a primary reason why health authorities recommend Paxlovid over molnupiravir when both are available and appropriate for the patient.
Subsequent observational studies have largely reinforced the findings from the original trials regarding their comparative effectiveness.
Dosing and Patient Eligibility
Both Paxlovid and molnupiravir are prescribed as a five-day course of oral pills taken twice daily. The Paxlovid dose consists of two nirmatrelvir tablets and one ritonavir tablet taken together. The standard dose for molnupiravir is 800 mg, taken as four capsules twice daily.
To be eligible for either treatment, treatment should begin as soon as possible and within five days of the first appearance of symptoms. The medications are authorized for individuals with mild to moderate symptoms who are not hospitalized. A patient must be considered at high risk for progressing to severe COVID-19 due to factors like age or underlying medical conditions.
While the general criteria are similar, there are differences in the specific populations authorized to take each drug. Paxlovid is authorized for adults and pediatric patients aged 12 and older who weigh at least 88 pounds (40 kg). Molnupiravir, however, is authorized only for adults aged 18 and older.
Contrasting Side Effects and Safety Concerns
The drugs have different safety profiles, particularly concerning interactions with other medications. Paxlovid contains ritonavir, which boosts the main antiviral but also inhibits a liver enzyme that metabolizes many common drugs. This creates a high risk of drug-drug interactions, potentially increasing other medications to unsafe levels, including certain statins, blood thinners, and some anti-seizure medications.
Reported side effects for Paxlovid are often mild, and these effects are temporary and resolve after the treatment course is completed. A healthcare provider must carefully review a patient’s current medications before prescribing Paxlovid to avoid harmful interactions. Side effects can include:
- An altered or metallic sense of taste (dysgeusia)
- Diarrhea
- Increased blood pressure
- Muscle aches
Molnupiravir’s safety concerns are of a different nature and do not involve the same drug-drug interaction profile as Paxlovid. The warnings for molnupiravir relate to its potential effects on bone and cartilage growth, which is why it is not authorized for use in patients younger than 18 years. There is also a concern regarding potential embryofetal toxicity based on findings from animal studies.
Due to these findings, molnupiravir is not recommended for use during pregnancy. Health authorities advise that women of childbearing potential should use effective contraception during treatment and for four days after the final dose. It is also recommended that men with partners of childbearing potential use reliable contraception during treatment and for at least three months after the last dose.