Home Medicines Paxlovid: effect, application, side effects (nirmatrelvir, ritonavir)

Paxlovid: effect, application, side effects (nirmatrelvir, ritonavir)

by Josephine Andrews
Published: Last Updated on 274 views

Paxlovid is a drug specifically designed to treat Covid-19. It is one of the antiviral drugs. Paxlovid consists of two active substances. This combination of active ingredients significantly slows down the virus multiplication in the human body. The drug has had provisional approval since January 2022. Read here what is known about the active ingredients, how they work and when doctors use Paxlovid in practice.

What is Paxlovid?

Paxlovid is a prescription drug used to treat Covid-19. It currently has provisional (conditional) approval for the European market.

Paxlovid is one of the antiviral drugs. That means it interferes with the ability of the coronavirus to multiply in the body. It can be taken in tablet form and consists of two active substances : nirmatrelvir (PF-07321332) and ritonavir .

This combination slows down the multiplication of Sars-CoV-2. This gives the body time to fight the corona virus on its own. This reduces the severity of the disease and shortens the duration of the disease. Ideally, inpatient hospital treatment can be averted for high-risk patients.

The main active ingredient , nirmatrelvir , is a so-called protease inhibitor and disrupts the function of a specific viral protein molecule (enzyme) that is urgently needed for the construction of new virus copies in the human cell.

The additional active ingredient ritonavir , on the other hand, slows down the degradation of nirmatrelvir in the human liver (inhibitor of cytochrome P450 / CYP3A4). This allows adequate amounts of nirmatrelvir to circulate and work in the body for a longer period of time.

Compared to other treatment options such as antibody therapies, Paxlovid has a major advantage: the drug is effective against all virus variants of Sars-CoV-2. This means that the mechanism of action is independent of the respective coronavirus variant .

How is Paxlovid used?

Paxlovid is intended for people aged 18 years and older who are at increased risk of severe disease. This applies in particular to immunocompromised, pre-existing or elderly patients in whom the effect of a vaccination is (severely) reduced.

Paxlovid treatment should ideally be started within five days of a confirmed Covid-19 diagnosis. The patents take the drug for five consecutive days. The daily dose consists of two tablets of nirmatrelvir (150 milligrams in the morning and evening) combined with one tablet of ritonavir (100 milligrams).

What side effects occur?

Since Paxlovid has only been available for a short time, the side effect profile and tolerability cannot yet be conclusively assessed. The health authorities are therefore monitoring it closely.

However, the regulatory documents indicate that one in ten people who received Paxlovid treatment experienced the following typical side effects:

  • Altered taste perception or taste disorders (dysgeusia)
  • Diarrhea
  • headache
  • Vomit

Interactions with other medicines possible

In particular, the sub-component ritonavir blocks important breakdown processes in the liver. Experts therefore suspect interactions with numerous drugs during the treatment period. Paxlovid should also not be taken in the case of severe liver and kidney disorders.

Interactions are suspected with certain:

  • Prostate medication (e.g.: alfuzosin)
  • Heart medications (e.g.: amiodarone, bepridil, dronedarone, propafenone, etc.)
  • Cholesterol-lowering drugs (e.g.: lovastatin, simvastatin, lomitapid, etc.)
  • Antihistamines (e.g.: astemizole, terfenadine, etc.)
  • Gout medication (e.g. colchicine)
  • Medications for erectile dysfunction ( sildenafil , avanafil, vardenafil, etc.)
  • Cancer drugs (e.g.: neratinib, venetoclax, etc.)
  • Antibiotics (e.g.: fusidic acid, etc.)
  • Painkillers, tranquilizers and migraine medications (e.g.: pethidine, diazepam , midazolam, dihydroergotamine, etc.)
  • Neuroleptics and antipsychotics (e.g.: lurasidone, pimozide, clozapine, etc.) and many more.

This list includes only a portion of drugs that may interact. The topic of drug interactions is therefore an important part of the medical consultation before possible Paxlovid treatment.

For the systematic recording of possible interactions, an online tool is available on the manufacturer’s website, which can be accessed via a QR code in the product information.

pregnancy and breast feeding period

There are no data on Paxlovid treatment during pregnancy. It is therefore not known whether the unborn child could be harmed by the active substances. According to the current state of knowledge, preliminary animal experiments do not provide any indications of embryotoxic effects of the main component nirmatrelvir.

However, the side agent ritonavir is suspected of being potentially harmful. Paxlovid should therefore not be used during pregnancy.

The regulatory documents also indicate that pregnancy should be avoided during the period of Paxlovid treatment (plus an additional seven days after stopping treatment).

The active substance ritonavir can reduce the effectiveness of hormonal contraception (“the pill ”).

It has not been studied whether Paxlovid can be excreted in human milk. A small number of studies indicate that at least ritonavir in small amounts could be able to do this. A risk to the newborn cannot therefore be completely ruled out. It makes sense to take a break from breastfeeding during the treatment period.

Immunocompromised patients

Taking Paxlovid in immunocompromised patients (HIV/AIDS) could potentially reduce the effectiveness of certain HIV medications. Clarify this in advance of a possible Paxlovid treatment with your doctor in order to work out an individual therapy plan.

How effective is Paxlovid?

The first reliable data on the effectiveness of Paxlovid are based on the interim results of the EPIC-HR pivotal study. According to this, Paxlovid can very effectively prevent severe courses or a fatal course of the disease in high-risk patients.

However, this only applies if the treatment is started within five days of the onset of the first symptoms.

The pivotal study enrolled subjects over the age of 18 who were symptomatic of COVID-19, had no supplemental oxygen needs, and had not been previously vaccinated or recovered. The majority of study participants were infected with the delta variant of the coronavirus.

As an additional inclusion criterion, the patients had to have at least one risk factor for a severe course: for example, obesity, diabetes, a chronic lung disease, a weakened immune system or cardiovascular disease.

Study participants were randomly (randomly) assigned equally to two groups: one group received Paxlovid treatment, which followed the treatment regimen described above, and the other group received placebo. In total, around 2,200 study participants were examined.

How does Paxlovid work?

In order to explain the mechanism of action of Paxlovid – more precisely of the actual main active ingredient nirmatrelvir – it is important to first explain the individual steps in the replication of the virus in the human cell.

Virus replication (in the infected human cell) involves, very simply, three basic steps:

  • Replication of the RNA genetic material of the virus.
  • Production of all virus proteins (from the existing viral genome) in the form of a “long protein chain” consisting of individual protein building blocks ( amino acids ).
  • Further processing: Specialized virus enzymes (endoproteases, specifically: the so-called 3CLpro-endopeptidase) cut this long amino acid chain into well-defined individual components at “predetermined breaking points”. Each of these protein fragments then takes on a specific function in the newly formed virus particle.

The nature and evolution of the virus has designed these newly created, shortened protein fragments in such a way that they spontaneously and precisely form new, fully functional (infectious) virus particles.

Experts refer to these finely tuned processes as “conserved mechanisms”. This means that they are absolutely identical for all Sars-CoV-2 variants – and thus an ideal target for drug development.

And Paxlovid? It interferes precisely with this conserved mechanism and fundamentally disrupts the production of the virus structural proteins described above. It specifically blocks the function of 3CLpro endopeptidase. If this viral enzyme can no longer cut the “long protein chain” into precisely fitting protein fragments, virus replication comes to a standstill.

What is conditional approval?

A conditional approval is a “provisional accelerated European market approval” under strict specifications and conditions for the manufacturer.

Such a status is only considered by health authorities if the drug is used to meet an urgent medical need – in the case of Paxlovid, to treat the potentially life-threatening Covid-19 disease.

As a rule, such an approval status is valid for one year and must be renewed annually. During this period, the manufacturer underpins the benefits and safety with further safety data and ongoing studies.

As soon as comprehensive data on the medicinal product is available and the risk-benefit assessment remains positive, this conditional approval will be converted into a regular full approval.

According to the current state of knowledge, the main component nirmatrelvir has a positive safety profile, which is only associated with mild general side effects.

Therefore, the European Medicines Agency (EMA) – despite known side effects of the secondary component ritonavir – came to the current assessment that the benefits of the combination product Paxlovid clearly outweigh the risks.

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