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Paxlovid: Most effective COVID treatment backed by WHO

M3 India Newsdesk Jun 15, 2022

The article talks about the use of Paxlovid as the most efficient COVID therapy which every doctor should know. The mechanism of action, dosage, administration and adverse effects of Paxlovid are also penned down in this article.

Paxlovid: What do we know

Paxlovid (nirmatrelvir and ritonavir) is the most recent COVID-19 therapy that has been making headlines. The Food and Drug Administration (FDA) approved an emergency use authorisation (EUA) in December for anybody aged 12 or older who weighs at least 40 kgs—and Pfizer just launched Phase 2 and 3 studies in children and adolescents ages 6 to 17.

Paxlovid is an oral antiviral medication that may be used at home in individuals who are at high risk for progression to severe COVID-19, significantly reducing the rates of hospitalisation or death.

Pfizer's medicine looks to offer a slew of advantages: It demonstrated an 85 per cent reduction in the risk of hospitalisation and death in the clinical trial that supported the EUA, a figure that prompted the National Institutes of Health (NIH) to prioritise it over other COVID-19 treatments; it is more affordable than many other COVID-19 treatments (it is provided free by the US government during a public health emergency); and, perhaps most reassuringly, it is expected to work against the Omicron variant.

This is the start of a game-changer. It is, in fact, our first effective oral antiviral medication for this virus. It has obvious value and has been shown to effectively avoid hospitalisation and mortality in high-risk individuals.

It's important to note that Paxlovid is not the only pill available to treat COVID-19; the FDA granted a EUA to Merck's molnupiravir (Lagevrio) in December, but some studies indicate that molnupiravir has a 30% reduction in the risk of hospitalisation and death from COVI

Additionally, this medicine is deemed more convenient than therapies such as remdesivir (which was authorised by the FDA in October 2020), which is delivered by intravenous (IV) injection.

FAQs on Paxlovid

1. What is Paxlovid's mechanism of action?

Paxlovid is a combination of two antiviral medicines. When you take your three-pill dosage, two of the tablets will contain nirmatrelvir, a medication that suppresses the replication of the SARS-CoV-2 protein. The other is ritonavir, which was once used to treat HIV/AIDS but is now used to increase the effectiveness of antiviral medications.

As a COVID-19 therapy, ritonavir basically inhibits nirmatrelvir's metabolism in the liver, allowing it to stay in your body longer giving it a boost to help fight the infection.

2. When should Paxlovid be administered?

Paxlovid must be started within five days after acquiring symptoms. As is the case with other antivirals, Paxlovid is most effective when started early in the course of an illness—in this instance, during the first five days after symptom onset. Once you've been unwell with the virus for more than a week, the antiviral cannot reverse the harm done to the body in a severe instance.

3. How often should I take Paxlovid?

Three Paxlovid tablets twice a day for five days total of 30 pills. It helps that the pills are placed on a "dose card," which is essentially a pharmaceutical blister pack that enables convenient pill punching.

4. Is Paxlovid available to anyone?

Paxlovid has been approved by the FDA for people aged 12 and older who weigh at least 88 pounds. However, you must also have a positive COVID-19 test result and be at high risk of developing severe COVID-19 to qualify for a prescription.

That implies you must either have specific underlying diseases (such as cancer, diabetes, obesity, or others) or be a senior citizen (nearly 81% of COVID-19 deaths occur in those over 65). According to the CDC, the more underlying medical issues a person has, the greater their chance of acquiring a severe case of COVID-19.The expectation is that the limits will gradually be loosened.

5. How effective is Paxlovid?

Pfizer cited results from a clinical study completed between mid-July and early December 2021 when it requested FDA approval. The research revealed that people who got Paxlovid (all of whom were unvaccinated) were 89 per cent less likely to experience serious illness or death than those who received a placebo. (While it is recommended to take Paxlovid after five days of symptom start, clinical trial patients took the medication within three days.) Scientists will continue to examine the drug's efficacy in real-world settings. WHO suggests against its use in patients at lower risk, as the benefits were found to be negligible.

6. How does Paxlovid work in children?

Pfizer initiated a clinical trial in March to evaluate Paxlovid's safety and effectiveness in children and adolescents ages 6 to 17 who exhibit COVID-19 symptoms and test positive for the virus but are not hospitalised or at risk for severe illness.

While Paxlovid is approved for use in adolescents and teens aged 12 and older who weigh minimum of 40 kgs, this age group was not included in the first clinical research. However, since many children attain the adult weight of 88 pounds, the FDA has granted EUA extensions for drugs such as monoclonal antibodies and remdesivir in lower age groups. According to the pharmacokinetics of the medications in Paxlovid, the variations in the metabolism and excretion of these pharmaceuticals in this age group, specifically, liver and kidney function are considered to be comparable to those in adults.

7. Is Paxlovid effective against Omicron?

Although Paxlovid's clinical studies were conducted before Omicron became prevalent, Pfizer asserts that the medicine is effective against the more infectious version. At least three laboratory-based studies have been undertaken so far to support this claim. Two of the studies were conducted by Pfizer, while the third was conducted in collaboration with Mount Sinai's Icahn School of Medicine. This research has not yet been peer-reviewed for publication in medical journals.

8. What are the possible adverse effects of Paxlovid?

Paxlovid should not cause substantial adverse effects in the majority of persons who use it. Paxlovid is often very well tolerated. The following are some of the most common adverse effects, which are typically mild:

  • Alteration or impairment of taste 
  • Diarrhoea 
  • Increased blood pressure 
  • Muscle pains

Due to Paxlovid's renal clearance, dosage modifications may be necessary for individuals with mild-to-moderate kidney illness. There are dosage adjustments for renal impairment:

  • In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min), the dosage of Paxlovid is 150 mg nirmatrelvir (one 150 mg tablet) and 100 mg ritonavir (one 100 mg tablet) twice daily for five days.
  • Patients with mild renal impairment (eGFR ≥60 to <90 mL/min) should receive the standard dose of 300 mg nirmatrelvir (two 150 mg tablets) and 100 mg ritonavir (one 100 mg tablet) with all three tablets taken together orally twice daily for five days.
  • Paxlovid is not recommended at this time in patients with severe renal impairment (eGFR <30 mL/min) renal illness or those with severe liver disease; the drug's concentrations may grow excessively high, resulting in greater adverse effects.

Molnupiravir may be another oral alternative for these people. It's worth mentioning that Paxlovid is currently under investigation, and so not all hazards are known.

9. Is it safe to take Paxlovid if I am also taking other drugs?

Paxlovid may interact with a large number of drugs, and in certain situations, physicians may choose not to prescribe Paxlovid due to the risk of catastrophic consequences.

Paxlovid interacts with a number of pharmaceuticals, including several anti-rejection medications used by transplant patients and other commonly prescribed medications such as those used to treat cardiac arrhythmias. Paxlovid also slows the metabolism of anticoagulants, or blood thinners, on which many elderly persons rely, resulting in dangerously high levels of those drugs in the body.

Additionally, it interacts with cholesterol-lowering drugs such as atorvastatin (Lipitor), although this interaction is less difficult for individuals to overcome. Nothing harmful will happen if you skip five days of Lipitor.

If you are pregnant or nursing, the FDA suggests that you consider your choices and unique circumstances with your health care practitioner, since there is no experience with the medicine in these groups. If you are pregnant or may get pregnant while taking Paxlovid, it is suggested that you utilise effective barrier contraception or abstain from sexual activity.

10. Any alternatives for Paxlovid, if I'm not eligible?

For patients who are unable to take Paxlovid possibly due to a pharmaceutical interaction, there are alternative medicines available, including molnupiravir, another oral medication, as well as sotrovimab and remdesivir, both IV medications.

For those at risk of severe illness, the NIH advises the following therapies in order:

  • Paxlovid
  • Sotrovimab (Xevudy)
  • Remdesivir (Veklury)

However, comparisons and rankings of this kind are problematic. None of these medications has been compared directly or with identical variations.

11.  Are vaccinations still required if Paxlovid is available?

Even as additional medications become available, vaccination remains a critical component of prevention. At the very least, vaccination, mitigating attempts such as masking, and testing would be necessary. Early testing is critical to the success of these medications.

Take a test even if you believe you are merely suffering from a cold or allergies and if you are able to get one. Home testing is a critical component of really 'operationalising' these drugs. While home tests are not as sensitive as laboratory-based polymerase chain reaction (PCR) testing, they are nonetheless very useful in diagnosing infections.

Paxlovid is not perfect, despite its great potency, and even if it were, viruses may change and acquire resistance to antiviral drugs. Will some individuals continue to be hospitalised? No drug is without flaws. However, for many people at high risk, this medicine may significantly lower that risk.

WHO pushes for Paxlovid

The World Health Organization (WHO) highly recommended Pfizer's Paxlovid for mild to moderately ill COVID-19 individuals who fall into high-risk categories but also urged steps to increase access to therapy in low- and middle-income nations.

The WHO said in a statement that the recommendation was based on fresh evidence from two randomised controlled studies involving 3,078 patients that indicated Paxlovid may reduce hospitalisation risk by 85 per cent in high-risk categories.

The WHO said that their guidance is applicable to people at the greatest risk of developing a serious illness, such as those who are unvaccinated, elderly, or immunocompromised. Additionally, it said that studies indicated that advantages were limited in low-risk people.

Paxlovid may prevent more hospitalisations than its alternatives, has fewer potential side effects than the antiviral drug Molnupiravir, and is easier to administer than intravenous options such as remdesivir and antibody treatments, according to the WHO's most recent guidelines on drugs for COVID-19 treatment.

However, the WHO expressed worry about two impediments to the drug's deployment in low- and middle-income nations. One is early testing and diagnosis since the medicine must be administered during the earliest stages of infection. The WHO cited statistics indicating that lower-income nations' average daily testing rate is one-eighth that of higher-income ones.

The second point of contention is the company's lack of clarity on availability and price information. Pfizer and the Medicines Patent Pool recently signed a licencing deal allowing a restricted number of nations to produce a generic version of the medicine, although none have reached the point of supply.

Status in India

Nineteen of the Medicines Patent Pool's (MPP) 35 sub-licensing agreements are with Indian companies, including Biocon Ltd in Bengaluru; Glenmark Pharmaceuticals, Sun Pharmaceuticals, and Cipla in Mumbai; Torrent Pharmaceuticals and Cadila Pharmaceuticals in Ahmedabad; Hetero Drugs and Laurus Labs in Hyderabad; and Emcure Pharmaceuticals in Pune.

Earlier this week, it was speculated that Hetero's medicine will be accessible in pharmacies very soon, but no confirmation was provided.

WHO said on April 22 that it was "very worried" that low- and middle-income nations may be placed at the "back of the line" for Paxlovid therapy, just as they had been with COVID-19 vaccines. It said that Pfizer's licence deal with the MPP restricted the number of nations eligible to profit from generic drug manufacturers.

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.

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