Pfizer’s Paxlovid first Covid pills to get US FDA nod, meant for mild-to-moderate cases

Paxlovid is a combination of two drugs — nirmatrelvir and ritonavir — & is approved for those who are at high risk of progressing to severe Covid, including hospitalisation or death.

Representational image | Pfizer world headquarters in New York | Commons

New Delhi: The US Food and Drug Administration issued an emergency use authorisation (EUA) for Pfizer’s Paxlovid for the treatment of mild-to-moderate Covid-19 in patients over 12 years of age and weighing at least 40 kilograms.

Paxlovid is a combination of two drugs — nirmatrelvir and ritonavir. Both these drugs are known as protease inhibitors. Proteases are enzymes that help break down proteins into smaller functional units in viruses, allowing them to carry out the functions required to infect a cell.

Both nirmatrelvir and ritonavir bind with specific proteases in the coronavirus and inhibits their functions.

Nirmatrelvir, also developed by Pfizer, works on a SARS-CoV-2 protein to stop the virus from replicating, while ritonavir slows down nirmatrelvir’s breakdown, to help it remain in the body for a longer period at higher concentrations.

The drug is approved for those who are at high risk of progressing to severe Covid-19, including hospitalisation or death.

Paxlovid is a prescription drug and should be administered as soon as possible after diagnosis of Covid-19 and within five days of symptom onset.

It is not authorised for use as a pre-exposure, prevention drug for Covid-19 or for those who have already progressed to severe or critical Covid-19.

Paxlovid is administered as three tablets — two tablets of nirmatrelvir and one tablet of ritonavir — taken together, orally, twice daily for five days, for a total of 30 tablets. It is the first oral antiviral of its kind to get EUA authorisation for treatment of Covid-19.

While there are some possible side-effects of the drug, and it can adversely impact the functioning of some other drugs (if taken together), the US Food and Drug Administration concluded that the benefits of Paxlovid outweigh its possible risks.

Benefits outweigh potential risks, FDA says

For issuing an EUA, the US FDA evaluates the scientific evidence available and carefully balances any known or potential risks, with any known or potential benefits of the product. It is different from a full FDA approval.

Based on its review, the FDA has determined that it is reasonable to believe that Paxlovid may be effective for the treatment of mild-to-moderate Covid-19 in authorised patients.

The agency has also determined that the known and potential benefits of Paxlovid outweigh the known and potential risks of the product.

There are currently no adequate, approved and available alternatives to Paxlovid for the treatment of Covid-19, according to the US FDA.

The clinical trial

The primary data supporting this EUA for Paxlovid came from a clinical trial called EPIC-HR, that studied Paxlovid for the treatment of non-hospitalised symptomatic adults with a laboratory confirmed diagnosis of SARS-CoV-2 infection.

Patients in the trial were adults, 18 years of age and older. They were either defined to be at higher risk of progression to severe disease or were 60 years and older.

None of the patients in the trial had received a Covid vaccine, neither had they been previously infected with the disease.

The trials showed that Paxlovid reduced the proportion of people with Covid-19 related hospitalisation or death by 88 per cent, compared to those who were given a placebo (any treatment that has no active properties for the purpose of comparison) within five days of symptom onset and who did not receive Covid-19 therapeutic monoclonal antibody treatment.

Contraindications and side-effects

Possible side effects of Paxlovid include impaired sense of taste, diarrhea, high blood pressure and muscle aches. Using Paxlovid at the same time as certain other drugs may result in potentially significant drug interactions.

Administering Paxlovid to those with uncontrolled or undiagnosed HIV-1 infection may lead to HIV-1 drug resistance.

Ritonavir may cause liver damage, so caution should be exercised when giving Paxlovid to patients with pre-existing liver diseases, liver enzyme abnormalities or liver inflammation.

Because Paxlovid works by inhibiting a group of enzymes that break down certain drugs, Paxlovid should not be used with drugs that are highly dependent on those enzymes to work.

Paxlovid is also not recommended to be used with drugs that strongly induce those same enzymes. This is because the enzymes can lead to the faster breakdown of nirmatrelvir or ritonavir. Reduced concentrations of nirmatrelvir or ritonavir may lead to the emergence of drug resistant variants of the virus.

Paxlovid cannot be started immediately after discontinuing such medications either, because the effects of those medications remain after discontinuation.

Paxlovid is not recommended in patients with severe kidney or severe liver impairment. In patients with moderate renal impairment, a reduced Paxlovid dose is needed.

(Edited by Poulomi Banerjee)