Is there a substitute for Paxlovid?: Exploring COVID-19 Antiviral Alternatives

October 12, 2025 •

4 min read

Since the FDA authorized oral antivirals for COVID-19 in late 2021, Paxlovid has become a primary treatment option for many high-risk individuals. However, because of its numerous drug interactions and eligibility limitations, understanding if there is a substitute for Paxlovid is crucial for managing the illness safely and effectively for certain patients.

Quick Summary

Alternatives to the antiviral Paxlovid for treating COVID-19 include the oral medication Lagevrio (molnupiravir) and the intravenous infusion Veklury (remdesivir), especially for high-risk patients with contraindications.

Key Points

Paxlovid Alternatives: Oral (Lagevrio/molnupiravir) and intravenous (Veklury/remdesivir) options are available for high-risk patients who cannot take Paxlovid for COVID-19.
Drug Interaction Issues: The primary reason for seeking a Paxlovid substitute is its significant risk of drug-drug interactions, which Lagevrio largely avoids.
Lagevrio Efficacy: While historically considered less effective, Lagevrio is a valid oral alternative when other treatments are unsuitable, with recent studies showing comparable effectiveness in specific populations.
Veklury Administration: Veklury requires three consecutive days of intravenous infusions in a clinical setting, making it less convenient than oral alternatives.
Personalized Treatment: A healthcare provider's consultation is essential to evaluate individual patient factors like concurrent medications, kidney function, and pregnancy status to select the safest and most effective antiviral.
Not for Hospitalized Patients: Oral antivirals are primarily for outpatient use in high-risk individuals to prevent severe disease, not for those already hospitalized with severe COVID-19.

For many years, Paxlovid has been a standard of care for treating mild-to-moderate COVID-19 in patients with risk factors for progression to severe disease. Its active ingredient, nirmatrelvir, works by inhibiting a key protease enzyme that the SARS-CoV-2 virus needs to replicate itself. The second component, ritonavir, boosts nirmatrelvir's effectiveness by slowing its metabolism. However, this ritonavir component is also the primary reason for Paxlovid's extensive list of potentially serious drug interactions with other common medications. For patients who cannot take Paxlovid, several effective alternatives exist, though they come with different considerations regarding efficacy, administration, and eligibility.

Oral Antiviral Alternative: Lagevrio (Molnupiravir)

Lagevrio, also known by its generic name molnupiravir, is an oral antiviral treatment for mild-to-moderate COVID-19. It is a viable alternative for adults aged 18 and older who are at high risk for severe COVID-19 and for whom other treatments, like Paxlovid and remdesivir, are unavailable or inappropriate.

How Lagevrio Works

Unlike Paxlovid's protease inhibitor mechanism, Lagevrio works by introducing errors into the virus's genetic code, a process called 'error catastrophe'. This prevents the SARS-CoV-2 virus from multiplying effectively within the body.

Considerations for Lagevrio

Efficacy: Initial studies showed Lagevrio to be less effective than Paxlovid, reducing the risk of hospitalization or death by about 30% compared to Paxlovid's nearly 90% in initial trials. Recent studies on newer variants, however, have shown comparable effectiveness in reducing hospitalization and death in high-risk patients.
Drug Interactions: A major advantage of Lagevrio is its significantly lower risk of drug interactions compared to Paxlovid, making it a safer option for patients on complex medication regimens.
Eligibility: It is authorized for adults only and should not be used during pregnancy due to potential fetal harm.

Intravenous Antiviral Alternative: Veklury (Remdesivir)

Veklury, the brand name for remdesivir, is an intravenous (IV) antiviral approved for treating COVID-19 in high-risk outpatients. It is considered a first-line alternative when Paxlovid is contraindicated due to drug interactions.

How Veklury Works

Veklury works by inhibiting a viral enzyme necessary for replicating the virus's genetic material. This mechanism is distinct from both Paxlovid and Lagevrio.

Considerations for Veklury

Efficacy: Veklury has demonstrated efficacy comparable to Paxlovid in reducing hospitalization and death in high-risk patients, especially when administered early.
Administration: Unlike the oral antivirals, Veklury requires a 3-day course of intravenous infusions, which must be administered in a healthcare setting like a hospital or infusion center. This can be a logistical challenge for some patients.
Eligibility: Approved for a wider range of patients than Lagevrio, including certain pediatric patients.

Comparison of COVID-19 Antivirals


Feature	Paxlovid (Nirmatrelvir/Ritonavir)	Lagevrio (Molnupiravir)	Veklury (Remdesivir)
Mechanism of Action	Inhibits the SARS-CoV-2 main protease. Ritonavir boosts nirmatrelvir levels.	Introduces errors into the viral RNA to prevent replication.	Inhibits an enzyme essential for viral RNA replication.
Administration	Oral pills, taken twice daily for 5 days.	Oral capsules, taken twice daily for 5 days.	Intravenous (IV) infusion for 3 days in a healthcare setting.
Efficacy	Highly effective (up to 88% reduction in hospitalization/death) when taken early.	Lower initial efficacy (around 30%) but recent data suggests effectiveness against current variants.	Highly effective, comparable to Paxlovid when given early.
Primary Limitation	Significant and complex drug interactions due to ritonavir.	Lower initial efficacy, authorized only when other options are unavailable or inappropriate.	Requires inconvenient IV administration in a clinical setting.
Patient Eligibility	Adults and pediatric patients (12+ years, ≥40 kg) at high risk.	Adults (18+ years) at high risk, when other options are not suitable.	Adults and pediatric patients (≥3.3 lbs) at high risk, including hospitalized patients.

Important Considerations for Choosing a Treatment

The choice of antiviral treatment is not one-size-fits-all and depends on numerous patient-specific factors. A healthcare provider will consider the following when recommending a treatment plan:

Current Medications: The potential for drug-drug interactions is the most common reason for needing a Paxlovid substitute. A healthcare provider will review all medications to assess compatibility.
Underlying Health Conditions: Certain conditions, such as severe kidney or liver impairment, may preclude the use of specific antivirals or require dose adjustments.
Pregnancy Status: Lagevrio is not recommended for use during pregnancy, and requires effective contraception for people of childbearing potential, while Paxlovid is considered safer for pregnant individuals, though limited data exist.
Logistics and Availability: Practical considerations, such as the ability to receive a 3-day intravenous infusion, can influence the choice between an oral pill like Lagevrio and Veklury.
Treatment Guidelines: National and local treatment guidelines, such as those from the Infectious Diseases Society of America (IDSA), provide clinical recommendations based on the latest evidence.

Conclusion

While Paxlovid is a highly effective treatment for mild-to-moderate COVID-19, it is not the only option available for high-risk patients. For individuals with contraindications due to drug interactions, or who are otherwise ineligible, equally effective or suitable alternatives exist. Oral Lagevrio (molnupiravir) offers a solution with fewer drug interactions but requires careful consideration of its comparative effectiveness and pregnancy warnings. Veklury (remdesivir) provides a powerful IV alternative, especially for those unable to take oral medications, though it requires access to an infusion center. It is essential for patients to consult with a healthcare provider to determine the most appropriate and safest course of treatment based on their individual health profile and circumstances.

Frequently Asked Questions

Initial trials showed Paxlovid was more effective, but more recent studies suggest that in high-risk populations, both Paxlovid and Lagevrio effectively reduce hospitalizations and death. A healthcare provider will weigh the most current data when making a recommendation.

The most common reason is the potential for serious drug-drug interactions with other medications. The ritonavir component in Paxlovid can interfere with many drugs, including certain heart medications, statins, and others.

Veklury is an intravenous (IV) infusion given over three consecutive days. It must be administered in a healthcare setting, such as a hospital or infusion clinic, rather than at home.

As of late 2025, Lagevrio (molnupiravir) is the primary oral alternative for outpatients who cannot take Paxlovid. Veklury is also an option, but it is an IV treatment.

Antiviral treatments like Paxlovid and remdesivir target parts of the virus that are less prone to mutation, meaning they are generally expected to remain effective against current and future variants, unlike many monoclonal antibody treatments.

Oral antivirals are intended for high-risk patients with mild-to-moderate COVID-19 who have symptoms within the past five days. High-risk includes older adults and those with certain health conditions.

Many older monoclonal antibody treatments are no longer recommended because the dominant COVID-19 variants have evolved to be resistant to them. Antivirals that target a different part of the virus are now the preferred option.