Paxlovid: A bad mix with epileptic drugs.

What is Paxlovid?

COVID-19 was a disease that changed all our lives. For around a year, we didn’t have a proper vaccine to this disease. The treatment was basically wait, support the patient and watch for complications, because as with many viral diseases, there is no specific cure. Doctors dabbled around with antivirals and steroids with some degrees of success. However, on December 22nd 2021, the United States Food and Drug Administration (FDA) approved the use of Paxlovid for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients, 12 years of age and older, weighing at least 40 kilograms. This gave hope to many patients looking for a simple oral treatment for COVID-19.

How does Paxlovid work?

The brand, Paxlovid, contains a mixture of two antiviral drugs: nirmatrelvir and ritonavir. The drug should be administered as soon as possible, upon being diagnosed with COVID-19. Both components of the drug inhibit an enzyme called protease in the coronavirus which helps it in replicating itself and creating more coronaviruses. Since it cannot create more of itself, the virus is attacked by the immune system and removed from the body. Nirmatrelvir is the main active component in inhibiting this enzyme, but nirmatrelvir is quickly broken down by a liver enzyme called cytochrome P450. Ritonavir by itself has antiviral activity like nirmatrelvir, but its main action is inhibiting the liver enzymes that break down nirmatrelvir. 

These liver enzymes are the secret of why Paxlovid can’t be used with anti-seizure drugs. It’s not all the same for every anti-seizure drug, but it depends on the interaction of the anti-seizure drug with the liver enzymes.

What are the drugs we should be vary of while using Paxlovid?

Some drugs such as carbamazepine, phenobarbital, phenytoin, and primidone are absolutely contraindicated, which means they cannot be used at all with Paxlovid. The reason is that, they increase the enzymes that break down Paxlovid (enzyme inducer), which means that it is broken down faster than it can work on viruses. The treatment will be ineffective and the scarier story is that the virus will gradually become Paxlovid-resistant if it’s exposed to a low level of drug as with the above. It’s basically like vaccinating the coronavirus against Paxlovid.

Some drugs can be used with caution like cenobamate, eslicarbazepine, oxcarbazepine, rufinamide, and topiramate. These are weak inducers and they potentially decrease the effectiveness of Paxlovid. It will still work, but not to the degree expected, so it’s best to use it with caution.

The liver process can occur vice versa as well. Paxlovid can occupy the functional breakdown space used by the liver, and it won’t let other drugs be degraded by cytochrome p450. Some examples are cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, ethosuximide, everolimus, felbamate, lacosamide, midazolam, oxcarbazepine, perampanel, stiripentol, tiagabine, and zonisamide. Here, Paxlovid itself is not affected, but the levels of the drugs mentioned, drastically rise up, sometimes maybe even to toxic life-threatening levels. The blood levels of these drugs should be monitored and used with extreme caution. Remember that this enzyme inhibition effect lasts even after you’ve stopped Paxlovid, so remember to mention it to your doctor.

Last but not least, Paxlovid has a funny relationship with lamotrigine, another drug used for seizures. Paxlovid actually induces and increases a subset of the liver enzymes which break down lamotrigine, causing lamotrigine levels to decrease in the bloodstream. So, if you need to treat epilepsy with lamotrigine, while using Paxlovid, you will need to measure and monitor blood lamotrigine levels closely.

What should we do if we need to treat epilepsy patients who have COVID-19?

If you really need to use Paxlovid for COVID-19, you can use an anti-seizure drug like levetiracetam (sold under the Keppra brand name) that are not involved with the liver. If you are using other anti-seizure drugs, you can use alternate antiviral drugs instead of Paxlovid, like molnupiravir or intravenous (IV) therapies like remdesivir. But the downside is that these two drugs have more side-effects, are less effective and more expensive than Paxlovid for a full course. 

You don’t need to be alarmed if you have both epilepsy and COVID-19. Tell your doctor honestly about all the drugs you are on, and they will adjust your treatment accordingly. There are always other roads we can travel on, if one road is closed. All you need to do is reach out and get the correct help.