What is Paxlovid?
Paxlovid is a prescription medicine for covid-19 treatment. It currently has a provisional (conditional) approval for the European market.
Paxlovid is one of the antiviral drugs. That is, it interferes with the ability of the coronavirus to replicate in the body. It can be taken in tablet form and consists of two active substances: Nirmatrelvir (PF-07321332) and Ritonavir.
The main active ingredient, nirmatrelvir, is a so-called protease inhibitor and interferes with the function of a specific viral protein molecule (enzyme) that is urgently needed for the construction of new viral copies in the human cell.
The additive ritonavir, on the other hand, slows down the breakdown of nirmatrelvir in the human liver (inhibitor of cytochrome P450 / CYP3A4). This allows sufficient amounts of nirmatrelvir to circulate and act in the body for longer periods of time.
How is paxlovid used?
Paxlovid is intended for people 18 years and older who are at increased risk of a severe course. This applies in particular to immunocompromised, previously ill or elderly patients in whom the effect of a vaccination is (severely) reduced.
The daily dose includes two tablets of nirmatrelvir (pink tablet) combined with one tablet of ritonavir (white tablet) each morning and evening. For each dose (that is, twice daily), take all three tablets together at the same time.
What are the side effects?
Because paxlovid has only recently become available, its side effect profile and tolerability cannot yet be conclusively assessed. The health authorities are therefore monitoring it closely.
- Altered taste perception or taste disturbances (dysgeusia)
- Diarrhea
- Headache
- Vomiting
Interactions with other medications possible
The partial component ritonavir in particular blocks important degradation processes in the liver. Therefore, experts suspect interactions with numerous drugs during the treatment period. Also, paxlovid must not be taken in cases of severe liver and kidney disorders.
Interactions are suspected with certain:
- Cardiac medications (e.g.: amiodarone, bepridil, dronedarone, propafenone, etc.)
- cholesterol-lowering drugs (e.g.: lovastatin, simvastatin, lomitapide, etc.)
- antihistamines (e.g., astemizole, terfenadine, etc.)
- gout medications (e.g. colchicine)
- erectile dysfunction medications (sildenafil, avanafil, vardenafil, etc.)
- cancer drugs (e.g.: neratinib, venetoclax, etc.)
- Antibiotics (e.g.: fusidic acid, etc.)
- Neuroleptics and antipsychotics (ex: lurasidone, pimozide, clozapine, etc.) and many more.
This list includes only a subset of medications where interactions may exist. The topic of drug interactions is therefore an important part of the physician’s educational discussion in advance of possible paxlovide treatment.
Pregnancy and lactation
No data are available on paxlovide treatment during pregnancy. Therefore, it is not known whether the unborn child could be harmed by the active ingredients. Preliminary animal studies provide no evidence of embryotoxic effects of the main ingredient, nirmatrelvir, based on current knowledge.
It is also clear from the registration documents that pregnancy should be avoided during the period of paxlovid treatment (plus a period of an additional seven days after discontinuation of treatment).
The active ingredient ritonavir can reduce the effect of hormonal contraception (“the pill”).
Immunocompromised patients
Taking paxlovide could potentially reduce the effectiveness of certain HIV medications in immunocompromised patients (HIV/AIDS). Clarify this with your treating physician in advance of possible paxlovide treatment to develop an individualized treatment plan.
How effective is paxlovid?
However, this only applies if treatment is started within five days of the onset of the first symptoms.
The pivotal study included over 18-year-old individuals who were symptomatic with Covid-19, had no supplemental oxygen requirements, and had not been vaccinated or recovered prior to the study. The majority of study participants were infected with the delta variant of coronavirus.
The study participants were randomly assigned in equal proportions to two groups: One group received paxlovide treatment following the treatment regimen described above, and the other group received placebo. In total, approximately 2,200 study participants were thus studied.
How does paxlovid work?
Virus replication (in the infected human cell) involves very simplified- three basic steps:
- Replication of the RNA genetic material of the virus.
- Production of all viral proteins (from the existing viral genetic material) in the form of a “long protein chain” consisting of protein individual building blocks (amino acids).
The nature and evolution of the virus has designed these newly formed shortened protein fragments precisely so that they spontaneously, precisely fit together to form new fully functional (infectious) virus particles.
Experts refer to these finely tuned processes as “conserved mechanisms.” This means that they are absolutely identical in all Sars-CoV-2 variants – and thus an ideal target for drug development.
What is a conditional approval?
A conditional approval is a “provisional accelerated European marketing authorization” under strict guidelines and conditions for the manufacturer.
Such status is only considered by health authorities if an urgent medical need is met by the drug – i.e., in the case of paxlovid, to treat the potentially life-threatening covid-19 disease.
As soon as comprehensive data on the drug are available and the risk-benefit assessment remains positive, this conditional approval will be converted into a regular full approval.
Based on current knowledge, a positive safety profile of the main ingredient nirmatrelvir is emerging, associated only with mild general side effects.
