Pfizer COVID-19 antiviral paxlovid authorised by MHRA

A second oral antiviral for the early treatment of COVID-19 has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA).

Paxlovid — a combination of two active ingredients, PF-07321332 and ritonavir — was approved after final trial results suggested a five-day treatment course reduced the risk of COVID-19-related hospitalisation and death within 28 days by 89% in high-risk adults with symptomatic COVID-19 infection, when compared with a placebo group in which treatment was started within 3 days of the onset of COVID-19 symptoms.

The treatment, which is taken as two separate tablets that are packaged and taken together, works by inhibiting the enzyme required for viral replication, keeping levels of virus in the body low and helping the body overcome infection. The addition of the antiretroviral ritonavir helps to slow the breakdown of PF-07321332 in the body, thereby increasing its effectiveness.

The MHRA recommends the use of paxlovid as soon as possible and within five days of the start of symptoms. It has been authorised for use in people aged 18 years and above who have mild-to-moderate COVID-19 infection and at least one risk factor for developing severe illness, such as obesity, older age (>60 years), diabetes mellitus or heart disease.

“We now have a further antiviral medicine for the treatment of COVID-19 that can be taken by mouth rather than administered intravenously. This means it can be administered outside a hospital setting, before COVID-19 has progressed to a severe stage,” said June Raine, chief executive of the MHRA.

“I hope the announcement gives reassurance to those particularly vulnerable to COVID-19, for whom this treatment has been approved. For these individuals, this treatment could be life-saving.”

A press release from the MHRA, published on 31 December 2021, said it was “too early” to know whether the Omicron variant had any impact on the effectiveness of paxlovid, but the organisation said it was “proactively working” with the manufacturer Pfizer to establish this.

The release also highlighted that the antiviral treatment “may interact” with certain medications. The MHRA has therefore advised that patients’ current medications are “carefully reviewed” before paxlovid is prescribed, and appropriate advice given on adjustments that may be needed to their current medications.

Penny Ward, visiting professor in pharmaceutical medicine at King’s College London, told The Pharmaceutical Journal that the summary of product characteristics (SmPC) for the treatment suggest the main side effects of paxlovid appeared to be an altered sense of taste, diarrhoea and vomiting.  

“There is [also] a need to reduce the dose in patients with moderate renal impairment: in the [United States] product information this is quantified as an [estimated glomerular filtration rate] between 30 and 60mL/minute.

“It might have been helpful for this additional information to be provided in the SmPC as many healthy individuals over the age of 65 [years] have reduced renal function just because of advancing age.”

However, Ward said the “main issue”, which could restrict potential use of the product in practice, was the list of drugs that are contraindicated in combination with paxlovid.

“These include several medicines commonly used by older people and those with other concomitant disorders; for example, ischaemic heart disease, which also confers higher risk of adverse outcomes from COVID-19,” she explained.

Ward added that, in people needing to take a variety of medicines for other disorders, the approved antiviral molnupiravir might be preferred above paxlovid.

Its approval means paxlovid will be added to the national ‘Platform adaptive trial of novel antivirals for early treatment of COVID-19 in the community’.