Paxlovid: available in pharmacies, composition, for whom?

[Mise à jour le 3 février 2022 à 14h41] Green light for Paxlovid, a treatment made by the laboratory Pfizer to be administered orally (in tablets) at the first signs of Covid infection in order to avoid serious forms. In a review dated February 2, 2022, the Directorate General for Health announces the availability of this antiviral in pharmacy (city and for indoor use in healthcare establishments), indicated “in adults not requiring oxygen therapy and being at high risk of progression to a severe form of COVID-19This medicinal product can thus be prescribed by any doctor provided that the latter complies with the obligations relating to early access. a statement on January 27, 2022, the European Medicines Agency (EMA) announced the conditional marketing authorization for Paxlovid. In France, on January 21, 2022, the High Authority of Health authorized this drug in early access for adults with Covid-19 not requiring oxygen therapy and at high risk of progression to a severe form of the disease. “This early access authorization is granted following the opinion of the ANSM having concluded on the basis of the evaluation of the preclinical and clinical data available at a favorable risk/benefit ratio presumed in the therapeutic indication” argues the HAS. It would reduce 85% the risk of having a severe form of Covid. The Paxlovid is the first treatment for Covid-19 which will be accessible in town and can be prescribed by general practitioners. Its mechanism of action “gives hope of sustained efficacy on the different variants, including Omicron”. This drug treatment comes in addition to vaccination “as a substitute”. “More broadly the implementation of anti-Covid-19 treatments, does not exempt patients from respecting barrier measures and physical distancing“ specifies the authority. The Paxlovid should be available in pharmacies “from the end of January” according to HAS. The HAS recommends setting up a follow-up cohort for this anti-Covid-19 treatment, which will aim to assess the immuno-virological and clinical efficacy in various groups of patients and to monitor the risk of emergence of potential resistance, particularly in immunocompromised patients. The HAS also hopes that clinical trials on this combination treatment can be set up soon. What is the composition Paxlovid? What is its function ? Its effectiveness against Covid? Its side effects?

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.

For whom is Paxlovid indicated?

Paxlovid treatment should be initiated within 5 days following the onset of Covid symptoms. To be eligible for early access, 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

When is Paxlovid available in France?

The Paxlovid is the first treatment for Covid-19 available in town pharmacies. It can be prescribed by general practitioners. Thursday, February 3, 2022, a first delivery operation of Paxlovid by the Pfizer laboratory is carried out with the depositories of Public Health France (SpF) in mainland France and Corsica. It is therefore possible to prescribe PAXLOVID®, from February 3, 2022 in France. The reception of the first treatments is possible from February 4, 2022 in pharmacies. For Overseas, given logistical constraints, prescription will be possible from February 7, 2022. On January 27, the European Medicines Agency announced the conditional marketing authorization for Paxlovid. Conditional Marketing Authorization (AMC) is used as an expedited authorization procedure to expedite drug approval during health emergencies. This generally concerns drugs that meet an unmet medical need on the basis of less complete data than those normally required. This occurs if the benefit of the immediate availability of a drug to patients outweighs the risk inherent in the fact that all the data are not yet available. This medication can be dispensed by:

• Community pharmacies in town on presentation of the prescription mentioning the bar code which will allow the pharmacist to ensure that the eligibility of the treatment has been validated by the prescriber. 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 visit and the start of symptoms.
• Pharmacies for indoor use in healthcare establishments for any patient treated within the establishment during a stay or a session.

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% (EPIC-HR study) after its 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 all, orally, 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 side effects ?

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 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®

HAS recalls that in the event of a contraindication, the use of the monoclonal antibody Xevudy is possible as a cure. In addition, prophylactic treatment with monoclonal antibodies Evusheld must be offered to eligible patients. The safety and effectiveness of PAXOLIVID in children under 18 years of age have not yet been established. No data is available.

What is the price ?

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.

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.