What is Paxlovid (nirmatrelvir/ritonavir)?

From the Guidelines

Paxlovid is an effective antiviral medication for treating COVID-19 in high-risk patients, consisting of nirmatrelvir and ritonavir, which can reduce the risk of hospitalization and death by approximately 89% in high-risk individuals, as supported by recent studies 1.

Key Points

• Paxlovid is a combination of nirmatrelvir (300mg) and ritonavir (100mg) taken together twice daily for five days.
• Treatment should begin within five days of symptom onset for maximum effectiveness.
• Paxlovid works by preventing viral replication, with nirmatrelvir blocking a key viral enzyme while ritonavir boosts nirmatrelvir levels in the body.
• Common side effects include altered taste, diarrhea, muscle aches, and high blood pressure.
• Paxlovid is not recommended for those with severe kidney or liver disease, and dosage adjustments are necessary for moderate kidney impairment.

Important Considerations

• Patients should inform their healthcare provider about all medications they take, including over-the-counter drugs and supplements, due to significant drug interactions with ritonavir.
• Some patients may experience "Paxlovid rebound," where symptoms temporarily return after completing treatment, but this generally resolves without additional intervention.

Recommendation

Based on the recent studies, Paxlovid is a recommended treatment option for high-risk patients with COVID-19, as it can significantly reduce the risk of hospitalization and death 1.

From the FDA Drug Label

PAXLOVID which includes nirmatrelvir, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro: also referred to as 3CLpro or nsp5 protease) inhibitor, and ritonavir, an HIV-1 protease inhibitor and CYP3A inhibitor, is indicated for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. PAXLOVID is nirmatrelvir tablets co-packaged with ritonavir tablets. Nirmatrelvir is a SARS-CoV-2 main protease (Mpro) inhibitor, and ritonavir is an HIV-1 protease inhibitor and CYP3A inhibitor

Paxlovid (nirmatrelvir/ritonavir) is a combination of two drugs:

• Nirmatrelvir: a SARS-CoV-2 main protease (Mpro) inhibitor
• Ritonavir: an HIV-1 protease inhibitor and CYP3A inhibitor It is indicated for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults who are at high risk for progression to severe COVID-19, including hospitalization or death 2.

From the Research

Definition and Composition of Paxlovid

• Paxlovid, also known as nirmatrelvir/ritonavir, is an oral antiviral treatment authorized for adults with mild-to-moderate COVID-19 who are at increased risk for progression to severe illness 3.
• It is a combination protease inhibitor that blocks replication of SARS-CoV-2, the virus that causes COVID-19 4.
• Paxlovid is composed of nirmatrelvir, a SARS-CoV-2 main protease inhibitor, and ritonavir, a human immunodeficiency virus type 1 protease inhibitor 5.

Mechanism of Action and Efficacy

• Nirmatrelvir works by inhibiting the main protease of SARS-CoV-2, preventing the virus from replicating 5.
• Ritonavir boosts the levels of nirmatrelvir in the body, allowing it to work more effectively 5.
• Studies have shown that Paxlovid is effective in reducing the risk of hospitalization and death in patients with mild-to-moderate COVID-19 3, 4, 6.
• Paxlovid has been shown to be noninferior to other treatments, such as VV116, in terms of time to sustained clinical recovery 7.

Indications and Usage

• Paxlovid is indicated for the treatment of mild-to-moderate COVID-19 in adults who are at risk for progression to severe illness 3, 5.
• It is recommended to start treatment within 5 days of symptom onset and to give it for 5 days' duration 5.
• Paxlovid is authorized for use in persons aged ≥12 years weighing ≥40 kg 5.

Safety and Drug Interactions

• Drug interactions are a major concern for nirmatrelvir-ritonavir, and it is recommended to carefully review potential interactions before starting treatment 5.
• Paxlovid has been shown to be generally safe and well-tolerated, but it can cause adverse events such as diarrhea, nausea, and headache 5.
• Recurrence of COVID-19 symptoms or a positive viral test result (COVID-19 rebound) has been reported in some patients after treatment with Paxlovid 4.