Nirmatrelvir/ritonavir
Nirmatrelvir/ritonavir, sold under the brand name Paxlovid, is a co-packaged medication used as a treatment for COVID-19. It contains the antiviral medications nirmatrelvir and ritonavir. It is taken by mouth. In December 2021, the co-packaged medication was granted emergency use authorization by the United States Food and Drug Administration (FDA) for the treatment of COVID-19. 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. The co-packaged medication was approved for medical  use in the United Kingdom in December 2021, and in both the European Union and Canada in January 2022. Medical uses. The co-packaged medication is indicated for the treatment of mild-to-moderate COVID-19 in people aged twelve years of age and older weighing at least 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. If administered within five days of symptom onset, the efficacy of the co-packaged medication against hospitalization or death in adults is about . In the European Union, the co-packaged  medication is indicated for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID-19. 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. Contraindications. The co-packaged medication is not recommended during pregnancy and in women who can become pregnant but who are not using contraception. Breastfeeding should be interrupted during treatment. These recommendations are because laboratory studies in animals suggest that high doses  of the co-packaged medication may affect the growth of the fetus. There are no human data on the use of nirmatrelvir during pregnancy related to the risk of birth defects, spontaneous abortions (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 the co-packaged medication. A temporary reduction in body weight was observed in the offspring of nursing rats . Adverse drug reactions. Co-administration with certain drugs may have serious effects and may sometimes be fatal. The drug is contraindicated in those with hypersensitivity to the two main components, with severely reduced kidney or liver function, co-administered with certain drugs, such as those dependent on CYP3A for removal for which a raised concentration results in serious reactions, or those with potent CYP3A inducers for which reduced blood concentration of the two main components may result in loss of effect against the virus and possible resistance, among others. Co-administration also affects the concentration of several drugs, sometimes requiring  changing the dose or careful monitoring. Many of these drugs are widely prescribed to people at high risk from COVID-19. Adverse effects. Adverse events of the co-packaged medication, 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%). Overdose. There is no specific antidote for overdose with the co-packaged medication, treatment consists of supportive measures such as monitoring of vital signs and observation of clinical status. Manufacturing. Pfizer selected its largest oral tablet factory in Freiburg im Breisgau as the launch facility for  the manufacturing of the co-packaged medication. Nirmatrelvir, the novel portion of the co-packaged medication, 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 the co-packaged medication on an industrial scale. Pfizer selected another factory in Ascoli Piceno, Italy, to assist the Freiburg factory with packaging tablets into blister packs. History. The primary data supporting the U.S. Food and Drug Administration (FDA) emergency use authorization for nirmatrelvir/ritonavir are from EPIC -HR, a randomized, double-blind, placebo-controlled clinical trial studying nirmatrelvir/ritonavir for the treatment of non-hospitalized symptomatic adults with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Participants were adults 18 years of age and older with a prespecified risk factor for progression to severe disease or were 60 years and older regardless of prespecified chronic medical conditions. All participants had not received a COVID-19 vaccine and had not been previously infected with COVID-19. The main outcome measured in the trial was the proportion of people who were hospitalized due to COVID-19 or died due to any cause  during 28 days of follow-up. Nirmatrelvir/ritonavir significantly reduced the proportion of people with COVID-19 related hospitalization or death from any cause by 88% compared to placebo among participants treated within five days of symptom onset and who did not receive COVID-19 therapeutic monoclonal antibody treatment. In this analysis, 1,039 participants had received nirmatrelvir/ritonavir, and 1,046 participants had received placebo and among these participants, 0.8% who received nirmatrelvir/ritonavir were hospitalized or died during 28 days of follow-up compared to 6% of the participants who received placebo. Society and culture. Economics. The U.S. secured 10million courses for  billion. A single course of Paxlovid costs around $529.50. Legal status. On 16 November 2021, Pfizer submitted an application to the U.S. Food and Drug Administration (FDA) for emergency use authorization for the co-packaged medication. The authorization was granted on 22 December 2021. The European Medicines Agency (EMA) issued guidance about the use of the co-packaged medication for the treatment of COVID-19 in the EU on 16 December 2021. The Israeli Ministry of Health approved the use of the co-packaged medication on 26 December 2021. South Korea approved the use of the co-packaged medication on  27 December 2021. The UK Medicines and Healthcare products Regulatory Agency (MHRA) granted conditional approval of the co-packaged medication in December 2021. Health Canada approved the use of the co-packaged medication in January 2022. The Singapore Health Sciences Authority approved the use of the co-packaged medication for treating adults in February 2022. In February 2022, China approved the medication for the treatment of adults who have mild to moderate COVID-19 and are at a high risk of progressing to a severe condition. Misleading comparison with ivermectin. The co-packaged medication 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. Research. In September 2021, Pfizer began a phase II/III trial of nirmatrelvir combined with ritonavir. 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 co-packaged medication against hospitalization or death in adults when administered within five days of symptom onset is about . In 2022, the PANORAMIC trial started testing the effectiveness of nirmatrelvir /ritonavir for treating COVID-19 infections.