Paxlovid, the latest miracle drug for COVID-19, should I stock up on one? Not everyone needs it!

This is the 4174th article of Da Yi Xiao Hu

In recent times, people across the country are experiencing the first wave of Omicron epidemic, and whether there is a treatment drug is undoubtedly what everyone is most concerned about.

According to news reports, on December 14, China National Pharmaceutical Group will be responsible for the import and distribution of Pfizer's novel coronavirus treatment drug Paxlovid (nematevir tablets/ritonavir tablets) in the Chinese mainland market within the next year. It was rumored that an Internet platform started selling it at a price of 2,980 yuan per box, but it was short-lived. Paxlovid was urgently removed from the shelves that night after the news came out.

So everyone in the circle of friends started asking around,

What? I heard this is a miracle drug with special effects, and it can restore you to full health after taking it?

What kind of medicine is this? Can everyone of us take it?

So, can someone help me get a box to stock up? After all, if I have medicine in hand, I won’t be panicked!

If it is positive, can the doctor prescribe this medicine for me?

Wait, is it necessary to take it? Are there any side effects?

Today let’s talk about Paxlovid and a few things you should know!

According to the editor, Paxloid was conditionally approved for import registration by the National Medical Products Administration on February 12 this year, and is currently a prescription drug sold only in hospitals. The main ingredients of this oral antiviral drug are namatevir and ritonavir, and it has been included in my country's 2022 "New Coronary Pneumonia Treatment Guidelines (9th Edition)", see the figure below.

1. How effective is Paxlovid?

----At present, Paxlovid's effectiveness data is higher than other new coronavirus drugs.

According to clinical trial data published in the New England Journal of Medicine in April 2022, among unvaccinated patients with mild to moderate COVID-19 who are at high risk of progression to severe illness, oral Paxlovid given within 3 days of symptom onset can significantly reduce the rate of hospitalization or death within the next 28 days by 89% compared with the control group given oral placebo.

Similarly, the results of studies on vaccinated people also confirm the effectiveness of Paxlovid. In November 2022, the Centers for Disease Control and Prevention reported a real-world study that included people who had been vaccinated or previously infected. Adults who took Paxlovid within 5 days of being diagnosed with COVID-19 had a 51% lower hospitalization rate in the next 30 days than adults who did not take the drug.

2. How does Paxlovid fight the new coronavirus?

----In short, two people with one mind can accomplish anything.

Paxlovid is an antiviral combination drug treatment consisting of two separate drugs - namatevir and ritonavir. Namatevir is an active ingredient that inhibits viral replication and can block a key enzyme required by the new coronavirus to replicate viral particles. In this way, the virus released from the cell cannot enter uninfected cells in the body, thereby blocking the infection. The other drug in Paxlovid is ritonavir, which can slow down the metabolism and decomposition of namatevir in the liver, thereby increasing the blood concentration of namatevir and its antiviral effect in the body.

3. Is Paxlovid the same as the anti-influenza drug Tamiflu?

---There are similarities and differences

We all know that Tamiflu is an antiviral drug for treating seasonal influenza and is effective against both influenza A and B viruses.

The common point of these two drugs is that Paxlovid and Tamiflu are both effective oral antiviral drugs that need to be taken early in the course of the disease. Tamiflu is also taken twice a day for 5 days, but it is generally hoped that it will be effective if it is started within 48 hours after the onset of flu symptoms. If it is taken beyond this time, it is unlikely to change the entire course of the disease. Paxlovid also needs to be taken within 5 days of onset.

However, the research data of Tamiflu tends to shorten the course of influenza, while the research focus of Paxloid is that it can significantly reduce the patient's progression to severe illness requiring hospitalization and death.

4. Can Paxlovid be used for all patients who test positive for COVID-19?

----The answer is no.

Currently, the U.S. FDA authorizes Paxlovid for use in people aged 12 years and older who weigh at least 40 kilograms, have a positive COVID-19 nucleic acid test result, and are at high risk of developing severe COVID-19 infection. All three conditions are met. For example, people with certain underlying diseases (including cancer, diabetes, obesity or other diseases), or people aged 65 years or older, because more than 81% of COVID-19 deaths occur in this age group). The U.S. Centers for Disease Control and Prevention believes that the more underlying diseases an individual has, the higher his risk of developing severe COVID-19.

In China, according to our country's 2022 "New Coronavirus Treatment Guidelines (9th Edition)", the high-risk groups for severe and critical illness include the following:

In summary, as a class representative, the following Covid-19 patients do not need to be treated with Paxlovid:

1. Asymptomatic Covid-19 infection

2. Symptomatic patients without risk factors for progression to severe illness

Therefore, we young and middle-aged people who are strong and healthy should stop worrying about stockpiling medicines, as it has nothing to do with us.

5. When should I start taking Paxlovid? How should I take it?

----It is recommended to start taking it within the first five days of the onset of symptoms, the earlier the better.

Like all other antiviral drugs, Paxlovid works best early in the disease, within the first five days after symptoms appear.

As shown in the figure below, the dosage is 2 times a day, once in the morning and once in the evening, 3 tablets (2 pink tablets of namatevir and 1 white tablet of ritonavir) orally each time for 5 consecutive days, and a total of 30 tablets are taken for the entire course of treatment. In addition, Paxlovid tablets should be swallowed whole and cannot be chewed, broken or crushed.

If you miss a dose of Paxlovid at the time you are supposed to take it, but it has not been more than 8 hours, you can take it immediately once you find it. If it has been more than 8 hours after the scheduled time, skip the dose and take the next dose at the original time. You cannot take 2 doses of the drug at a time.

6. Does Paxlovid prevent infection with the new coronavirus?

---Unfortunately, Paxlovid has not been found to have a preventive effect so far.

Paxlovid does not prevent individuals from being infected with the new coronavirus. It is currently mainly used to treat mild and common cases within 5 days of onset and adults with high risk factors for progression to severe illness.

7. Are there any adverse reactions to Paxlovid?

---For most people, the adverse reactions of Paxlovid are relatively mild and there are no serious side effects.

Possible adverse reactions include altered or impaired taste, diarrhea, occasional muscle aches, indigestion, vomiting, dizziness, and elevated liver enzymes.

However, you should stop taking Paxlovid and call your doctor if you experience any of the following signs of an allergic reaction: rash, difficulty swallowing or breathing, swelling of your mouth, lips, or face, tightness in your throat, or hoarseness.

Since Paxlovid is excreted through the kidneys, patients with mild to moderate kidney disease need to adjust their dose according to their doctor's advice. However, Paxlovid is generally not recommended for patients with severe kidney disease, those undergoing dialysis, or those with severe liver disease, because drug levels may be too high, leading to increased side effects.

8. Does Paxlovid affect patients’ usual medications?

---Paxlovid may interact with multiple drugs and affect efficacy. Doctors will instruct patients to temporarily stop taking the drug, change the drug or adjust the dosage according to the situation.

However, in some cases, drug interactions may cause serious complications, so your doctor may recommend not using Paxlovid if you are taking medications that are contraindicated with Paxlovid.

The following is a list of contraindications extracted from the Chinese version of Pfizer's Paxlovid instructions for your reference:

In short, when you see a doctor, you need to tell your doctor about the medications you are currently taking, including prescription drugs and over-the-counter drugs. The doctor will tell the patient whether it is safe to take Paxlovid while using other medications.

9. How much is Paxcovid sold for in China and abroad?

One box of Paxloid is enough for a 5-day course of treatment. In the United States, one box of Paxlovid costs $530 (about RMB 3,703), while in my country it costs RMB 2,300 per box, and has been temporarily included in medical insurance reimbursement.

Facts you need to know about the Paxlovid

1.How is the efficacy of the Paxlovid?

In the clinical trial published in April 2022, it had demonstrated an 89% reduction in the risk of hospitalization and death in unvaccinated people who were at high risk for progression to severe Covid-19 receiving treatment in 3 days after symptom onset.

Studies in people who have been vaccinated also confirmed the effectiveness of Paxlovid. In November 2022, the CDC reported on a real-world study that showed adults who took Paxlovid within five days of a COVID-19 diagnosis had a 51% lower hospitalization rate within the next 30 days than those who were not given the drug.

2.How does Paxlovid work?

Paxlovid is an antiviral therapy that consists of two separate medications packaged together--- nirmatrelvir and ritonavir. Nirmatrelvir is the key factor to fight the virus, which inhibits a key enzyme that the COVID virus requires in order to make functional virus particles. After nirmatrelvir treatment, the COVID virus that is released from the cells is no longer able to enter uninfected cells in the body, which, in turn, stops the infection. The other is ritonavir, it reduces nirmatrelvir's metabolism in the liver. As a result, nirmatrelvir's anti-viral works longer in the body to fight against the infection.

3.Is Paxlovid similar to Tamiflu?

As we know, Tamiflu is an antiviral drug that we use to treat seasonal flu and is effective for Flu A and Flu B.

Paxlovid and Tamiflu are both oral antiviral pills should be given early in the beginning. Tamiflu is taken twice a day for five days, and it must be started within 48 hours of onset. Paxlovid is required to be started in the first 5 days of symtoms occur.

Clinical data available for Tamifly mainly focused on whether Tamiflu could shorten the length of flu illness, whearas research concentrate on preventing severe type caused hospitalization and death.

4.Can anyone who has a positive COVID-19 test get a Paxlovid?

The FDA authorized Paxlovid for people ages 12 and older who weigh at least 88 pounds. But in order to qualify for a prescription, you must also have had a positive COVID-19 test result and be at high risk for developing severe COVID-19.

That means you must either have certain underlying conditions (including cancer, diabetes, obesity, or others) or be 65 or older (more than 81% of COVID-19 deaths occur in in this group). The more underlying medical conditions a person has, the higher their risk for developing a severe case of COVID-19, according to the CDC.

5.When should I start Paxlovid? How do I take Paxlovid?

It has been recommended that Paxlovid shoule be taken within five days of developing symptoms. Like all antivirals, Paxlovid works best early in the course of an illness—in this case, within the first five days of symptom onset.

You take 2 pink nirmatrelvir tablets and 1 white ritonavir tablet together at the same time twice daily for five days for a full course that adds up to 30 pills. Swallow the tablets whole. Do not chew, break, or crush the tablets.

If you miss a dose of PAXLOVID within 8 hours of the time it is usually taken,

take it as soon as you remember. If you miss a dose by more than 8 hours, skip

the missed dose and take the next dose at your regular time. Do not take 2

doses of PAXLOVID at the same time.

6.Does Paxlovid prevent Covid-19 infection?

No. Paxlovid doesn't prevent you from catching Covid-19. It is used to treat mild to moderate Covid-19 in people with positive viral testing and who are at high risk of progression to severe Covid-19.

7.What are the side effects from Paxlovid?

Most people who take Paxlovid should not experience serious side effects. Possible side effects include an altered or impaired sense of taste, diarrhea, increased blood pressure, muscle aches, abdominal pain, and nausea.

But people should stop taking Paxlovid and contact health care provider right away if they experience signs of an allergic reaction: skin rash, trouble swallowing or breathing

swelling of the mouth, lips, or face, throat tightness, hoarseness.

Since Paxlovid is cleared by the kidneys, dose adjustments may be required for patients with mild-to-moderate kidney disease. For patients with severe kidney disease—or who are on dialysis—or those with severe liver disease, Paxlovid is not recommended; the levels of the drug can become too high and could cause increased side effects.

8.Does Paxlovid interact with other medications I am taking?

There is a long list of medications Paxlovid may interact with and doctors will give advice to patient whether there is a need to temporarily discontinue the medications, change the medication, or regulate the dosage. While in some cases, doctors may not prescribe Paxlovid because these interactions may cause serious complications. The following lists are the contraindications from Pfizer Paxlovid fact sheet.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your doctor can tell you if it is safe to take Paxlovid with other medicines.

PAXLOVID is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions :

·Alpha1-adrenoreceptor antagonist: alfuzosin

·Antianginal: ranolazine

·Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine

·Anti-gout: colchicine

·Antipsychotics: lurasidone, pimozide

·Benign prostatic hyperplasia agents: silodosin

·Cardiovascular agents: eplerenone, ivabradine

·Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine

·HMG-CoA reductase inhibitors: lovastatin, simvastatin

·Immunosuppressants: voclosporin

·Microsomal triglyceride transfer protein inhibitor: lomitapide

·Migraine medications: eletriptan, ubrogepant

·Mineralocorticoid receptor antagonists: finerenone

·Opioid antagonists: naloxegol

·PDE5 inhibitor: sildenafil (Revatio®) when used for pulmonary arterial hypertension (PAH)

·Sedative/hypnotics: triazolam, oral midazolam

·Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin

·Vasopressin receptor antagonists: tolvaptan

PAXLOVID is contraindicated with drugs that are potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer:

·Anticancer drugs: apalutamide

·Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin

·Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor

·Antimycobacterials: rifampin

·Herbal products: St. John's Wort (hypericum perforatum)

References:

1. General Office of the National Health Commission of the People's Republic of China, General Office of the State Administration of Traditional Chinese Medicine of the People's Republic of China. Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Version 9) [EB/OL]. (2022-03-15). http://www.nhc.gov.cn/cms-search/downFiles/ef09aa4070244620b010951b088b8a27.pdf

2.Hammond J, Leister-Tebbe H, Gardner A, et al. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med 2022; 386:1397-1408. DOI: 10.1056/NEJMoa2118542

3.Shah MM, Joyce B, Plumb ID, et al. Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19 — United States, April–September 2022. MMWR Morb Mortal Wkly Rep 2022;71:1531–1537. DOI: http://dx.doi.org/10.15585/mmwr.mm7148e2.

4.https://www.pfizermedicalinformation.cn/products/package-insert/paxlovid

5. https://www.yalemedicine.org/news/13-things-to-know-paxlovid-covid-19

6.https://labeling.pfizer.com/ShowLabeling.aspx?id=16670

7.https://labeling.pfizer.com/ShowLabeling.aspx?id=16474

Author: Doctor of Pediatrics, School of Medicine, University of Melbourne, Australia

Pediatrician at ParkwayHealth (China)

Jiang Benran