askST: What do we know about the oral antiviral drugs used to treat Covid-19?

SINGAPORE - Health Minister Ong Ye Kung said on July 5 that all polyclinics and more primary care clinics here can now prescribe oral antiviral drugs to eligible Covid-19 patients.

This is to ensure that most people who have contracted Covid-19 can be treated outside of hospitals, even as coronavirus cases rise, driven by the latest Omicron subvariants BA.4 and BA.5.

These oral tablets are now available at all the polyclinics in Singapore as well as at more than 103 Public Health Preparedness Clinics (PHPCs).

Elsewhere, Australia has just widened access to these oral antiviral drugs from July 11 so that more people, including all Australians aged over 70 who test positive for Covid-19, can access them.

The Straits Times answers some questions you may have about these drugs:

A: Singapore's Health Sciences Authority (HSA) has authorised the emergency use of two oral treatments for Covid-19.

The first is Pfizer's Paxlovid, which is a combination of nirmatrelvir and ritonavir tablets. HSA approved it under the Pandemic Special Access Route on Jan 31 and by March 24, it was available at three polyclinics and 20 PHPCs.

The second one is molnupiravir, which has the brand name Lagevrio and is developed by MSD - known as Merck in the United States. HSA gave the authorisation on April 19.

Both oral antivirals help to reduce the risk of hospitalisation and death.

A: The oral treatments are meant for those aged 18 and above who have tested positive for Covid-19, have mild to moderate symptoms and are at high risk of becoming very sick. These include people who are immunosuppressed, have risk factors such as heart failure or diabetes, or are fighting a cancer.

These oral antiviral tablets are available only via prescription. Treatment must be started within five days of the onset of Covid-19 symptoms - the earlier, the better.

Paxlovid is given as a course of three tablets (two tablets of nirmatrelvir and one tablet of ritonavir), to be taken twice a day for five days.

Treatment with Lagevrio - or molnupiravir - requires that you take four tablets twice a day, for five days.

A: Antivirals work by stopping the coronavirus from spreading in the body.

Paxlovid contains nirmatrelvir, which targets the 3CL-like protease, a key enzyme the coronavirus needs to replicate, and ritonavir, which helps to keep nirmatrelvir active in the body for longer by inhibiting its breakdown.

Molnupiravir works by inducing mutations in the viral RNA, stopping the virus from replicating.

A: Both Paxlovid and Lagevrio have been shown to be effective in reducing hospitalisation and death from Covid-19, though the latter has a lower efficacy.

Lagevrio has been shown to reduce the risk of hospitalisation and death among people at risk of developing severe Covid-19 by 30 per cent.

In contrast, Paxlovid has been shown to reduce the risk of hospitalisation and death in high-risk patients by nearly 88 per cent when given within five days of symptom onset.

Generally, Lagevrio may be considered as an alternative, if Paxlovid is not suitable for the patient. HSA has said that Lagevrio may be suitable for patients who are at risk of progressing to severe Covid-19 but not suited for the other available treatment options.

Dr Leong Hoe Nam, an infectious diseases physician at Rophi Clinic, said that Paxlovid has been shown to be effective against coronaviruses, including variants of Sars-Cov-2, but a big worry is that it can interact with many drugs, including cholesterol medicine, anti-depressants and the blood thinning medication warfarin.

Paxlovid is also not suitable for those with severe kidney disease. So, those who need the drug may not be able to use it, he said.

Molnupiravir was not designed to treat Covid-19, but it can potentially attack all kinds of RNA viruses, regardless of their mutations, and does not have any known drug interactions, said Dr Leong.

It is, however, not recommended for pregnant women, women who are breastfeeding, or those below 18 years of age.

"With molnupiravir, you do not have to worry about undiagnosed kidney issues or unknown drug interactions, but you have to contend with a lower efficacy," said Dr Leong.

He said he prescribes oral antivirals to those who are showing symptoms and have at least one risk factor for severe Covid-19, such as a serious heart condition, chronic obstructive lung disease, obesity or cancer.

People over the age of 60 are considered to be at risk of severe disease, even if they are fully vaccinated and boosted against Covid-19, but doctors would assess their health and symptoms before prescribing the drugs.

A: Some people, including President Biden's top medical advisor Dr Anthony Fauci, had reported falling sick again between two and eight days after their initial recovery.

Still, Dr Fauci said in late June that the drug did what it was supposed to do by keeping him out of hospital.

In a late May advisory, the US' Centers for Disease Control and Prevention said that a brief return of symptoms may be part of the natural history of a Sars-CoV-2 infection, and had nothing to do with the Paxlovid treatment or one's vaccination status.

It added that there was no evidence that additional treatment was needed.

"The hypothesis is that the body's immune system hasn't kicked in sufficiently to suppress the virus," said Dr Leong.

"The medicine just helps control the infection but it doesn't totally wipe out the virus in the first five days. It is up to the immune system to provide a second level of defence, but in some individuals, it kicks in later."