dm+d

Unassigned

Lactation Safety Information

Moderate amount of published evidence shows low amounts of ritonavir in breast milk resulting in variable infant serum levels, ranging from undetectable to low. No adverse effects reported in breastfed infants to date.
No published evidence relating to use of nirmatrelvir in breastfeeding, but it is likely to pass into breast milk.
Paxlovid is administered as a short course, and nirmatrelvir and ritonavir both have a short half-life, so risk of accumulation in the infant is low.
The manufacturer’s advise that breastfeeding is not recommended during treatment with Paxlovid and for 7 days after the last dose. This is to ensure any infant exposure via breast milk is completely avoided.
As a precaution monitor infant for poor feeding, adequate weight gain, vomiting, diarrhoea, poor sleeping, and signs of jaundice.
Breastfeeding can continue with COVID-19 infection.
Further advice is available from the UK Drugs in Lactation Advisory Service .
10 February 2022

New Medicines

Paxlovid Coronavirus disease 2019 (COVID-19) treatment in non-hospitalised adults at high risk of progression, with low dose ritonavir

Information

Paxlovid
New molecular entity
Pfizer
Pfizer

Development and Regulatory status

Launched
Approved (Licensed)
Pre-registration (Filed)
January 2022
Jan 22Licensed in the EU for treatment of coronavirus disease 2019 (COVID-19) in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID 19 [15].
Jan 22The indication approved by the MHRA is treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progression to severe COVID-19 [14].
Jan 22Available in UK [13].
Jan 22Paxlovid will be available in the UK via DHSC central distribution. Paxlovid is packaged in cartons containing 5 daily-dose foil blister cards. Each daily blister card contains 4 nirmatrelvir 150mg tablets and 2 ritonavir 100mg tablets. Total 30 tablets per carton [9,10].
Jan 22Recommended for EU conditional approval by CHMP “for the treatment of COVID-19” [8].
Dec 21MHRA grants a Conditional Marketing Authorisation for Paxlovid [7].
Dec 21EMA start rolling review of Paxlovid [5].
Dec 21EMA’s CHMP advises on emergency use of Paxlovid for the treatment of COVID-19. Treatment can be considered for adults with COVID-19 who do not require supplemental oxygen and who are at increased risk of progressing to severe disease, starting as soon as possible after diagnosis of COVID-19 and within 5 days of the start of symptoms . The two active substances (PF-07321332 and ritonavir), which are available as separate tablets, should be taken together twice a day for 5 days [5].
Dec 21US FDA approves emergency use of paxlovid as an at-home treatment for mild-to-moderate COVID-19 in high-risk patients aged 12 and over who weigh at least 40kg [6].
Nov 21In the US, Pfizer has announced it is seeking Emergency Use Authorization (EUA) from the FDA for Paxlovid (PF-07321332/ritonavir) for the treatment of mild to moderate COVID-19 in patients at increased risk of hospitalisations or death. The submission includes clinical data from the PII/III EPIC-HR interim analysis. Rolling submission of non-clinical data for Paxlovid was initiated with the FDA in Oct 2021. Pfizer has already started manufacturing the drug and has said it could have enough to cover 100,000 to 200,000 people by the end of the year. If the EUA is approved, the US government is expected to unveil plans to buy 10 million courses at an assumed purchase price of $500-per-course. Pfizer has also signed a voluntary licensing agreement with the Medicines Patent Pool (MPP) to help expand access, pending regulatory authorisation or approval, in 95 low- and middle-income countries [3].
Nov 21Pfizer plan to submit an EUA application to US FDA as soon as possible [2].

Category

SARS-CoV-2-3CL protease inhibitor
Coronavirus disease 2019 (COVID-19) is a new pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most cases are mild respiratory illnesses. However, around 20% require hospitalisation, mostly due to pneumonia, and can progress quickly to severe acute lung injury and acute respiratory distress syndrome (ARDS), which is associated with high mortality.
Coronavirus disease 2019 (COVID-19) treatment in non-hospitalised adults at high risk of progression, with low dose ritonavir
Oral

Further information

Yes

Trial or other data

Feb 22PIII RCT (NCT04960202; n=2246) found treatment of symptomatic Covid-19 with nirmatrelvir and ritonavir reduced risk of progression to severe Covid-19 vs placebo (incidence 0.77% with 0 deaths vs.7.01% with 7 deaths placebo group; relative risk reduction 89.1%; p<0.001) without evident safety concerns [12].
Feb 22Results of PII/III study (NCT04756531) are published in NEJM [11].
Dec 21Pfizer announces final results from an analysis of all 2,246 adults enrolled in its Phase II/III EPIC-HR trial. These results were consistent with the interim analysis, showing PF-07321332/ritonavir significantly reduced the risk of hospitalization or death for any cause by 89% compared to placebo in non-hospitalised, high-risk adult patients with COVID-19 treated within three days of symptom onset. In a secondary endpoint, PF-07321332/ritonavirreduced the risk of hospitalization or death for any cause by 88% compared to placebo in patients treated within five days of symptom onset, an increase from the 85% observed in the interim analysis. The EPIC-HR data have been shared with the U.S. Food and Drug Administration (FDA) as part of an ongoing rolling submission for Emergency Use Authorization (EUA) [4]
Nov 21Pfizer announce positive results from PII/III EPIC-HR study. Scheduled interim analysis found treatment with PF-07321332/ritonavir showed an 89% reduction in risk of COVID-19-related hospitalisation or death from any cause compared vs. placebo in patients treated within three days of symptom onset (primary endpoint); 3/389 patients (0.8%) in treatment group were hospitalised through day 28 following randomisation (with no deaths) vs. 27/385 (7.0%) in placebo group (with 7 subsequent deaths); p<0.0001. At the recommendation of an independent Data Monitoring Committee, further enrolment in the study will cease [2].
Jul 21PII/III study in which subjects with coronavirus disease 2019 (COVID-19) will receive PF-07321332/ritonavir or placebo orally every 12 hours for 5 days starts (NCT04960202). 3000 adults will be recruited in several countries including US and EU. Primary outcome is proportion of participants with COVID-19 related hospitalisation or death from any cause at day 28. Collection of primary outcome data is expected to compete December 21 [1].

Evidence based evaluations