Decision

Summary of the Public Assessment Report (PAR) for Paxlovid 150 mg/100 mg film-coated tablets

Updated 26 October 2022

The Public Assessment Report summarises the initial assessment at the time of approval in December 2021. The text in the original report remains unchanged.

Our advice is regularly updated on the basis of significant new data and our latest advice can be found in the Summary of Product Characteristics.

Lay summary, Paxlovid 150 mg/100 mg film-coated tablets (nirmatrelvir and ritonavir)

This is a summary of the Public Assessment Report (PAR) for Paxlovid 150 mg/100 mg film-coated tablets. It explains how this product was assessed and its authorisation recommended, as well as its conditions of use. It is not intended to provide practical advice on how to use this product.

This product will be referred to as Paxlovid in this lay summary for ease of reading.

For practical information about using Paxlovid, patients should read the Patient Information Leaflet (PIL) or contact their doctor or pharmacist.

What is Paxlovid and what is it used for?

This application is a full-dossier application. This means that the results of pharmaceutical, non-clinical and clinical tests have been submitted to show that this medicine is suitable for treating the specified indication.

Paxlovid is used for the treatment of COVID-19 in adults who do not require supplemental oxygen. It is only used in patients who are at increased risk for progression to severe COVID-19, including hospitalisation or death.

Patients must talk to their doctor if they do not feel better or if they feel worse while on treatment with Paxlovid.

How does Paxlovid work?

Paxlovid stops SARS-CoV-2, the virus that causes COVID-19 from multiplying . This can help the body to overcome the virus infection and may help the patient get better faster.

Paxlovid contains the active ingredients nirmatrelvir (formerly,PF 07321332) and ritonavir. Nirmatrelvir works by blocking the activity of an enzyme needed by the virus to multiply. Ritonavir (a protease inhibitor), slows the breakdown of nirmatrelvir, enabling nirmatrelvir to remain in the body for longer at levels that can stop the virus multiplying.

How is Paxlovid used?

Paxlovid consists of two different film-coated tablets: nirmatrelvir tablets and ritonavir tablets that are co-packaged together. The route of administration is by mouth.

The recommended dose is 2 tablets of nirmatrelvir with 1 tablet of ritonavir twice daily (a dose in the morning and a dose in the evening).

The blister foil (direct packaging of the tablets) for each day of treatment is divided into two different coloured sections to indicate which tablets need to be taken at each time of day - one side for the dose in the morning (AM dose) and the other side for the dose in the evening (PM dose).

A course of treatment lasts 5 days. For each dose, the patient should take all 3 tablets together at the same time. For patients with poor kidney function the advice is to take two tablets for 5 days. The treating doctor’s advice should be followed. The tablets should be swallowed whole and should not be chewed, broken or crushed. Paxlovid can be taken with or without meals.

Paxlovid is used for treating mild-to-moderate COVID-19.

Paxlovid is licenced for use in adults.

For further information on how Paxlovid is used, refer to the PIL and Summary of Product Characteristics (SmPC) available on the Medicines and Healthcare products Regulatory Agency (MHRA) website.

This medicine can only be obtained with a prescription.

The patient should always take the medicine exactly as their doctor/pharmacist has told them. The patient should check with their doctor or pharmacist if they are not sure.

What benefits of Paxlovid have been shown in studies?

Paxlovid has been studied in non-hospitalised symptomatic adult patients with COVID-19 who have at least one prespecified risk factor of progressing to severe COVID-19. Paxlovid significantly reduced the proportion of participants with COVID-19 related hospitalisation or death by 89.1%, compared with placebo.

What are the possible side effects of Paxlovid?

For the full list of all side effects reported with this medicine, see Section 4 of the PIL or section 4.8 of the SmPC available on the MHRA website.

If a patient gets any side effects, they should talk to their doctor, pharmacist or nurse. This includes any possible side effects not listed in the product information or the PIL that comes with the medicine. Patients can also report suspected side effects themselves, or a report can be made on behalf of someone else they care for, directly via the Yellow Card scheme at https://coronavirus-yellowcard.mhra.gov.uk or search for ‘MHRA Yellow Card’ online. By reporting side effects, patients can help provide more information on the safety of this medicine.

The most common side effects with Paxlovid (which may affect more than 1 in 100 but less than 1 in 10 people) are:

• Diarrhoea
• Vomiting
• Altered sense of taste

Why was Paxlovid approved?

It was concluded that Paxlovid has been shown to be effective in the treatment of COVID-19 (caused by SARS-CoV-2) in adults who are at risk for developing severe illness. Furthermore, the side effects observed with use of this product are considered to be acceptable for this type of treatment. Therefore, the MHRA and CHM concluded that the benefits are greater than the risks and recommended that this medicine can be approved for use.

Paxlovid has been granted a Conditional Marketing Authorisation (CMA). CMAs are intended for medicinal products that address an unmet medical need, such as a lack of alternative therapy for a serious and life-threatening disease. CMAs may be granted where comprehensive clinical data is not yet available, but it is judged that such data will become available soon.

What measures are being taken to ensure the safe and effective use of Paxlovid?

As for all newly authorised medicines, a Risk Management Plan (RMP) has been developed for Paxlovid. The RMP details the important risks of Paxlovid, how these risks can be minimised, any uncertainties about Paxlovid (missing information), and how more information will be obtained about the known risks and uncertainties.

‘Drug interactions with CYP3A4 substrates and CYP3A4 inhibitors’ is included in the RMP as an important identified risk of Paxlovid. Areas of missing information include safety of Paxlovid in patients with active liver impairment; use during pregnancy and pregnancy outcomes; use during breastfeeding and whether there are any adverse effects on the breastfed child; and the possible emergence of viral variants that are resistant to treatment and effectiveness against viral variants of concern.

All suspected side effects reported by patients and healthcare professionals will be continuously monitored. Any new safety signals identified will be reviewed, and if necessary, appropriate action will be taken to minimise the risk to patients.

Routine pharmacovigilance activities include the monitoring and assessment of adverse drug reaction reports (ADRs) and signal detection. The company will compile and submit to MHRA monthly summary safety reports for Paxlovid. If there are any reports of exposures to Paxlovid during pregnancy, the company has in place a detailed follow-up questionnaire to ensure that all relevant information about the exposure, the pregnancy and the outcome is captured for full assessment of the case.

In addition to routine pharmacovigilance activities, the Company has committed to carry out further studies including a study to assess the safety and tolerability of the product in patients with moderately impaired liver function and in patients with normal liver function; and a post-authorisation safety study in pregnant and breastfeeding women. The Company has committed to implementing an antiviral surveillance programme and will also assess the feasibility and usefulness of conducting a study to provide information on the emergence of viral variants in patients treated with Paxlovid.

Information about a medicine, including the known side effects and how to manage them is provided in the product information for healthcare professionals (the Summary of Product Characteristics or ‘SmPC’) and patients (the Patient Information Leaflet or ‘PIL’). The SmPC and PIL are routine risk minimisation measures. No additional risk minimisation measures are necessary for Paxlovid.

Other information about Paxlovid

A Conditional Marketing Authorisation for Paxlovid was granted in Great Britain (GB, consisting of England, Scotland and Wales) on 31 December 2021.

The full full public assessment report for Paxlovid is available in the downloadable PDF.

This summary was last updated in February 2022.