Pfizer’s Paxlovid drug is indicated against Covid infection, reducing the risk of hospitalization by 85%. Among the reported adverse effects, arterial hypertension was reported in 5 people treated. Efficacy, indications, drug interactions, price… The point.
In its latest report published on September 2, 2022, the Medicines Agency reports 103 side effects reported after using Paxlovid: 64% are non-serious effects, 30% are serious effects and 6% are deaths. Among the known effects: taste alterations and gastrointestinal disorders. But a new signal is “to be investigated”: high blood pressure. 5 cases have been recorded since Paxlovid’s follow-up began. For the most part, the hypertension was transient. A single serious case was notified in a septuagenarian who had to be hospitalized for dyspnoea and malignant hypertension, in a context of myeloma treated with the drug Kyprolis. The ANSM, however, believes that “the role of Paxlovid appears less likely than that of Kyprolis, which is known to increase blood pressure“. Nevertheless, this signal must be watched closely. The Paxlovid is a drug manufactured by the laboratory Pfizer to be administered orally (in tablets). The prescription is done at the first signs of infection covid in order to avoid serious forms. It is available since February 2022 in Francein pharmacies. On April 25, 2022, the High Authority of Health (HAS) had spoken in favor of reimbursement of this treatment. The Paxlovid features contraindications check before taking. This drug treatment comes in addition to vaccination, not as a replacement. What is the composition Paxlovid? What indication? How effective against Covid? With what medicines should it not be taken (dangerous drug interactions)? What is his price ? His reimbursement? Its side effects?
Definition: what is Paxlovid?
The American pharmaceutical company Pfizer developed antiviral treatment, marketed under the name of Paxlovid made up of nirmatrelvir and of ritonavir. It comes in the form of tablets to be taken as soon as possible after the positive diagnosis for Covid-19 and maximum within 5 days following the onset of symptoms. This treatment targets the enzyme necessary for viral replication, the 3C-like protease, and by inhibiting its action, it blocks the replication of SARS-CoV-2 in the body. A Marketing Authorization (AMM) was granted to it on January 28, 2022.
What are the indications for Paxlovid against Covid?
Paxlovid treatment is reserved for people at risk of severe forms of Covid-19. It must be initiated in 5 days following the onset of Covid symptoms. To be eligible, the patient must meet all of the following criteria:
- Be at least 18 years old
- Have a positive SARS-CoV-2 test (RT-PCR or antigen)
- Appearance of first symptoms attributable to COVID-19 disease < 5 days
- Patient not requiring oxygen therapy due to COVID-19
- Patient at high risk of progression to a severe form of COVID-191
- Absence of contraindication to treatment
- Risk of drug interactions assessed and initiation of treatment deemed possible by the prescriber
- Patient clearly informed of the procedures for implementing this treatment
How to get Paxlovid in pharmacies?
The Paxlovid is the first treatment for Covid-19 available in town pharmacies. It can be prescribed by general practitioners since February 3, 2022. Community pharmacies in town on presentation of the prescription mentioning the bar code which allows the pharmacist to ensure that the eligibility of the treatment has been validated by the prescribing doctor. The order is placed by the pharmacist after delivery of the prescription by the patient. Thus, to take into account supply times and respect the taking of the drug within 5 days after the onset of symptoms, it is necessary for the patient to go quickly to the community pharmacist after the medical consultation and the start symptoms.
How effective is it against Covid and against Omicron?
According to the High Authority for Health, Paxlovid “retains antiviral activity on the different variants“. “The data available to assess the efficacy of this treatment have demonstrated a reduction in the risk of progression to a severe form of Covid-19 (hospitalization or death) by approximately 85.2% after his administration.” In addition, the mechanism of action of Paxlovid gives hope of maintained efficacy on the various variants, including Omicron. Preliminary in vitro data indeed suggest that the variants of concern currently circulating are susceptible to treatment.
What is the composition of Paxlovid?
Paxlovid is composed of two molecules:
► The first PF-07321332 is the active agent that prevents the virus protein from replicating.
► The second is ritonavir, a protease inhibitor, normally used for the treatment of HIV infections. “HIV is not related to coronaviruses and the replication of its genetic material occurs through a different mechanism. But it produces him too a poly-protein that must be cut 9 times per a protease to form new viral particles“, Explain an article published in the scientific journal Medicine Science in June 2020.
Paxlovid would prevent the coronavirus protease from replicating.
A protease is a virus-specific enzyme which acts on viral proteins to promote the replication of the virus. To stop the replication of a virus, it is therefore necessary to reduce or prevent the protease from acting. Coronaviruses have two proteases, one of which is called SARS-CoV-2, 3CL. It is on this protease that the oral treatment Paxlovid acts.
What is the dosage of Paxlovid?
The recommended dosage for PAXLOVID® is 300mg PF-07321332 (2 tablets of 150 mg) and 100mg ritonavir (1 tablet of 100 mg), which must be taken together (3 tablets in allorally, 2 times a day for 5 days). PAXLOVID can be taken with or without food. The tablets should be swallowed whole and should not be chewed, broken or crushed. It must be administered as soon as possible after obtaining a positive result in a direct virological screening test for SARS-CoV-2 (PCR or TAG) and at the latest within 5 days of the appearance of the symptoms. symptoms.
What are the drug interactions of Paxlovid?
Concomitant use of PAXLOVID is contraindicated with certain treatments. Dosage adjustment or temporary discontinuation of certain other medications may be considered for the duration of antiviral therapy.
What are the side effects of Paxlovid?
Among the patients who participated in thePfizer study published in November 2021 and who received Paxlovid, 1.7% experienced serious adverse events and had to stop treatment. The active substance contained in this medication, ritonavir, can indeed cause side effects such as:
- diarrhea,
- nausea and vomiting
- abdominal pain
- sore throat or cough,
- headaches and dizziness
- skin rashes and itching
- disturbances in the metabolism of sugars and fats with abnormal fat redistribution observed after several months of treatment (called lipodystrophy)
- toxicity to the liver (increase in transaminases) and the pancreas.
What are the contraindications of Paxlovid?
The antiviral is contraindicated in people with severe hepatic impairment or severe renal impairment (eGFR < 30 ml/min), including patients with end-stage renal disease on haemodialysis. Dosage adjustment is necessary in patients with moderate renal impairment. Furthermore, it is not not recommended to use Paxlovid during pregnancy and in women of childbearing potential not using contraception. Breast-feeding should be discontinued during treatment with PAXLOVID® and, as a precaution, for 7 days after the end of treatment. The use of ritonavir may reduce the effectiveness of combined hormonal contraceptives. Patients using combined hormonal contraceptives should be advised to use an effective alternative method of contraception or an additional “barrier” method of contraception during treatment with PAXLOVID® and until the menstrual cycle following discontinuation of PAXLOVID®
What is the price of Paxlovid?
The price of the Paxlovid pill is not known. Nevertheless, Pfizer announced, in its press release, tiered pricing based on each country’s income level in order to guarantee equitable access to all and an affordable price. In other words, high- and upper-middle-income countries will pay more than low-income countries. The specialty PAXLOVID® (PF-07321332 150 mg/ ritonavir 100 mg film-coated tablets) is distributed free of charge health establishments and pharmacies. The user therefore benefits from this in a fully supported manner.
What reimbursement for Paxlovid?
On April 25, 2022, HAS decided in favor of reimbursement for this treatment. “It confirms the progress made by this medicinal product by awarding it a level 3 improvement in actual benefit (ASMR). Registration for reimbursement of this treatment should facilitate the prescription of Paxlovid® in community medicine and therefore its access for patients. In addition, general practitioners can rely on the Rapid Responses published by the HAS to prescribe this drug” specifies the authority in a press release.
Sources
– Covid-19: early access granted to Paxlovid® as a curative treatment. HAS. Press release January 21, 2022.
– PFIZER’S NOVEL COVID-19 ORAL ANTIVIRAL TREATMENT CANDIDATE REDUCED RISK OF HOSPITALIZATION OR DEATH BY 89% IN INTERIM ANALYSIS OF PHASE 2/3 EPIC-HR STUDY, November 5, 2021.
– Targeting the major protease of SARS-CoV-2 to manufacture an effective drug against this coronavirus, Medicine Science, June 2020.