What we know about Paxlovid (nirmatrelvir and ritonavir): oral antiviral against COVID-19 | New COVID-19 Medicine

Article reviewed by Dr. Jan de Witt

Paxlovid is an antiviral administered orally to patients who are ill with COVID-19 or have been exposed to the coronavirus SARS-CoV-2 and are at risk of developing severe illness. The manufacturer, pharmaceutical and biotechnology giant Pfizer, developed it to potentially help patients avoid severe illness which can lead to hospitalization and death. It is meant to be administered at the first sign of infection.

Paxlovid is not yet available, but is under evaluation by regulatory bodies around the world like FDA (in the United States) and EMA (in the European Union). Learn more by jumping to the section "Accessing Paxlovid”.

What is Paxlovid (nirmatrelvir and ritonavir)?

Paxlovid (nirmatrelvir and ritonavir) is an orally administered medication designed to stop the coronavirus SARS-CoV-2 from replicating by blocking the activity of a key enzyme that the virus uses to replicate inside cells.

A course of treatment consists of 30 pills administered over five days. The treatment can take place at home, it’s not necessary for a patient to be under supervision in a hospital over the course of the treatment.

How does Paxlovid (nirmatrelvir and ritonavir) work?

Mechanism of action

Paxlovid consists of two protease inhibitors, nirmatrelvir and ritonavir. Nirmatrelvir is designed to block the coronavirus SARS-CoV-2 from multiplying, while ritonavir slows the breakdown of nirmatrelvir in the body in order for it to remain active in the body for a longer time and at higher concentrations to help combat the virus.

Protease inhibitors are commonly used to treat HIV and hepatitis C. The origins of Paxlovid date back to the SARS epidemic in 2003 when nirmatrelvir started being investigated as a potential therapy in combination with ritonavir (a booster of other protease inhibitors, commonly used with HIV medications and approved in the US for the purpose in 1996) and since the COVID-19 pandemic, 210 researchers have worked on Paxlovid for SARS-CoV-2.

Clinical trial

The latest clinical trial conducted by Pfizer on Paxlovid included 1219 adults from clinical trial sites across North and South America, Europe, Africa, and Asia. Trial participants were elderly or had an underlying health condition which increased the risk of serious illness and had mild to moderate symptoms of COVID-19. Participants were randomised 1:1, with half being administered a Paxlovid pill and the other half receiving a placebo pill every 12 hours for a total of five days, starting treatment within three days of developing symptoms.

According to Pfizer, it found that, among participants who were administered the drug within three days from the onset of symptoms, the risk of COVID-19 related hospital admission or death was 89% lower in the Paxlovid group than the placebo group. When including participants who started the treatment on the fourth or fifth day, Paxlovid reduced the risk of hospitalization or death by 85%. Overall, 0.8% of those given Paxlovid were hospitalised, compared with 7% of patients who were given a placebo, and 0 deaths occurred among patients who received Paxlovid, while 1.6% of the patients who received placebo died.

Safety concerns

The combination of nirmatrelvir and ritonavir might be difficult to tolerate by some people due to ritonavir’s potential to affect how other medications are metabolized by the body. Many medicines should not be administered at the same time as Paxlovid, such as drugs for heart disease, immune conditions or pain relievers as they can cause interactions.

Molnupiravir, another COVID-19 pill, has caused concerns among experts due to a study that suggests that it could cause mutations in human DNA (while it’s designed to only cause mutations in virus RNA). There is no evidence of nirmatrelvir causing DNA genetic mutations according to preclinical studies.

What is the approval status of Paxlovid (nirmatrelvir and ritonavir)?

On December 16, 2021, the European Medicines Agency (EMA) has issued advice on the use of Paxlovid. This means it is not yet authorised in the EU, but can be used to treat adults with COVID-19.

The Food and Drug Administration (FDA), USA has issued an emergency use authorization (EUA) on December 22, 2021. The issuance of an EUA is different than an FDA approval. It means that the FDA has evaluated all the available scientific evidence and compared any known or potential risks with benefits. The FDA has determined that it is reasonable to believe that Paxlovid may be effective to treat COVID-19.

Paxlovid has been approved in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) on December 31, 2021. The medicine was found to be safe and effective by the MHRA in reducing the risk of hospitalisation and death in people with mild to moderate COVID-19 infection.

Health Canada has approved Paxlovid on January 17, 2022. Canada has placed an order for an initial quantity of one million treatment courses, with an option to buy up to 500,000 more.

The Therapeutic Goods Administration (TGA), Australia has given provisional approval on January 20, 2022. This means Pfizer must continue to provide information to the TGA on longer-term efficacy and safety from ongoing clinical trials and post-market assessment.

Accessing Paxlovid (nirmatrelvir and ritonavir)

Paxlovid is currently approved by the EMA for the European Union, the FDA in the United States, the MHRA in the UK, Health Canada in Canada and the TGA in Australia. Even if it takes longer to get approved in your country, once it has approval somewhere in the world, you will be able to access it as there are regulations that allow for medicines to be imported in countries where they are not currently approved.

Patients with life-threatening or debilitating diseases have the right to access, purchase, and import medicines with the help of their treating doctors.

Patients and their doctors can do this on the compassionate use or named patient import regulations basis, a legal exception of the general rule that a medicine can normally only be accessed after market authorisation/approval (whatever wording we use) in the country where the patient lives. This exception allows patients to in a legal, ethical and safe way access and get medicines that are not yet approved in their country.

Read more about the "named patient basis” here (EMA).

We are currently making efforts into sourcing molnupiravir so we can help you access Paxlovid (nirmatrelvir and ritonavir) no matter where you live.

Upcoming medicines for COVID-19

In November 2021, the EMA recommended authorising Ronapreve (casirivimab/imdevimab) and Regkirona (regdanvimab) for mild to moderate COVID-19 illness.

Other drugs under review by the EMA are:

• Kineret (anakinra)
• Lagevrio (molnupiravir)
• Olumiant (baricitinib)
• RoActemra (tocilizumab)
• Xevudy (sotrovimab)
• Evusheld (tixagevimab / cilgavimab)