In December 2021, the combination was granted emergency use authorization by the US Food and Drug Administration (FDA) for the treatment of coronavirus disease COVID-19. The co-packaged medications are sold under the brand name Paxlovid. Paxlovid is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in those requiring hospitalization due to severe or critical COVID-19.
On 31 December 2021, the UK Medicines and Healthcare products Regulatory Agency (MHRA) approved the combination "for people with mild to moderate COVID-19 who are at high risk of developing severe COVID-19".
Paxlovid is indicated for the treatment of mild-to-moderate coronavirus disease (COVID-19) in people aged twelve years of age and older weighing at least 40 kilograms (88 lb) with positive results of direct SARS-CoV-2 testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death. The co-packaged medication is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in those requiring hospitalization due to severe or critical COVID-19.
There are no human data on the use of nirmatrelvir during pregnancy related to the risk of birth defects, miscarriage or adverse outcomes. There are also no human data on the presence of nirmatrelvir in human milk, its effects on milk production or the infant. In pregnant rabbits, a reduction in fetal body weight was observed with systemic exposure 10 times higher than the authorized human dose of Paxlovid. A temporary reduction in body weight was observed in the offspring of nursing rats.
Nirmatrelvir/ritonavir is not recommended during pregnancy, and breastfeeding should be stopped during treatment.
Adverse drug reactionsEdit
Co-administration with certain medications may result in serious and sometimes fatal interactions. The drug is contraindicated in those with hypersensitivity to nirmatrelvir or ritonavir, with severely reduced kidney or liver function, co-administered with certain drugs, such as those dependent on CYP3A for clearance for which an elevated concentration results in serious reactions, or those with potent CYP3A inducers for which reduced plasma concentration of nirmatrelvir or ritonavir may result in loss of virologic response and possible resistance, among others. Co-administration also interferes with the concentration of several drugs, sometimes requiring dose adjustment or careful monitoring.
Adverse events of Paxlovid, regardless of causality, observed in the phase II-III EPIC-HR study included dysgeusia (4.8%–6%), diarrhea (3%–3.9%), vomiting (1.3%), hypertension (1%), and myalgia (1%).
Pfizer selected its largest oral tablet factory in Freiburg im Breisgau as the launch facility for the manufacturing of Paxlovid. The drug was first developed in the United States and was initially manufactured in small amounts in Groton, Connecticut to support clinical trials, but the Freiburg facility in Germany was responsible for figuring out how to mass produce Paxlovid on an industrial scale.
Pfizer also asked other factories to assist the Freiburg factory with the task of packaging Paxlovid tablets. For example, in December 2021, it was reported that the Pfizer factory in Ascoli Piceno was adding 100 workers to its existing workforce of 800 and switching to 24/7 operations to support two Paxlovid blister pack production lines coming online in February 2022.
Society and cultureEdit
The UK placed an order for 250,000 courses in October 2021, Australia pre-ordered 500,000 courses of the drug, and the US secured 10 million courses for $5.295 billion. Only 65,000 doses were allocated for shipment to U.S. states in December 2021.
On 16 November 2021, Pfizer submitted an application to the U.S. Food and Drug Administration (FDA) for emergency use authorization for the combination. The authorization was granted on 22 December 2021. The European Medicines Agency (EMA) issued guidance about the use of Paxlovid for the treatment of COVID-19 in the EU on 16 December 2021. The Israeli Ministry of Health approved the use of Paxlovid on 26 December 2021. South Korea approved the use of Paxlovid on 27 December 2021. The UK Medicines and Healthcare products Regulatory Agency (MHRA) granted conditional approval of Paxlovid on 31 December 2021.
Misleading comparison with ivermectinEdit
The combination is sometimes falsely claimed to be a "repackaged" version of the antiparasitic drug ivermectin, which has been promoted as a COVID-19 therapeutic. Such claims, sometimes using the nickname "Pfizermectin", rely on superficial similarities between the mechanism of action of both drugs and the claim that Pfizer is suppressing the benefits of ivermectin. To be effective against COVID-19, the concentration of ivermectin in the blood would require a dose that is 10-20 times higher than is safe.
In December, Pfizer completed a Phase III study of nirmatrelvir combined with ritonavir.
On 14 December, Pfizer announced that the result of the Phase II/III study of nirmatrelvir combined with ritonavir results showed a reduced risk of hospitalization or death.
On 31 December, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) approved the use of nirmatrelvir combined with ritonavir for adults who have mild to moderate infection and are at high risk of their illness worsening.
The efficacy of the combination against hospitalization or death in adult outpatients when administered within five days of symptom onset is about 88% (95% CI, 75–94%).
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