How do you know if your drug is likely to interact with Paxlovid, which is one of the anti-viral drugs for SARS-CoV-2
You can ask your Doctor?
They may go to the latest advice for the NHS and for some MS drugs you get the “avoid like the plague message” given in Doctory language. We know that paxlovid can affect the breakdown of some drugs and this is because it contains an anti viral drug called ritonavir.
Ritonavir inhibits cytochrome p450 enzymes called CYP3A4 and CYP2D6 meaning that any drug that is broken down by CYP3A4 that is taken at the same time as ritonovir, it will now not be broken down as quickly and so the effects of the drug may be enhanced and this could be dangerous if the drug is potentially toxic. Sidenafil is broken down by CYP3A4 so if you had sidenafil and paxlovid you may have something for a long, long time…P.S. Sidenafil is also known as Viagra, which is used to treat heart problems:-).
You could go to a drug checker site. Here is one from a “Drug Interaction Checker”
Check out cladribine and paxlovid and there is no issue, do the same with siponimod and there is no issue but now do ritonavir and you get a warning. That’s not good as paxlovid contains ritonovir.
OK, so let’s go to another trusted site The Liverpool COVID-19 Drug interactions checker and oh dear it doesn’t have cladribine, or siponimod or fingolimod or dimethyl fumarate or etc despite by being funded by an MS drug manufacturer:-( So that is not going to help.
You can do your own Searching
So the way you check the interactions with CYP3A4 and 2D6 is to Read the label in the US or the Summary of (medical) Product characteristics in Europe
Search (product name) and INN and label. This gives you sites to look at you can choose the FDA site if you live in the US (www..accessdata.fda.gov) or EMA sites in Europe (www.ema.europa.eu › medicines › human › EPAR). This should give you accesss to a pdf.
Press Control (Ctrl) f together which is the search function and then type in CYP and the search function with find every time CYP is mentioned
For cladribine it says (pg 14)
“Cladribine is not a relevant substrate (target) to cytochrome P450 enzymes and does not show significant potential to act as inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1
and CYP3A4. Inhibition of these enzymes or genetic polymorphisms (e.g. CYP2D6, CYP2C9 or
CYP2C19) are not expected to result in clinically significant effects on cladribine pharmacokinetics or
exposure. Cladribine has no clinically meaningful inductive effect on CYP1A2, CYP2B6 and
so this says cladribine’s breakdown will not be affected by ritonavir’s action on CYP3A4 or CYP2D6
For Siponimod (EMA) it says
“Siponimod is metabolised primarily by cytochrome P450 2C9 (CYP2C9) (79.3%) and to a lesser
extent by cytochrome P450 3A4 (CYP3A4) (18.5%)…….Because of a significant increase in exposure to siponimod, concomitant use of siponimod and medicinal products that cause moderate CYP2C9 and moderate or strong CYP3A4 inhibition is not recommended. This concomitant drug regimen can consist of a moderate CYP2C9/CYP3A4 dual inhibitor (e.g. fluconazole) or a moderate CYP2C9 inhibitor in combination with a separate moderate or strong CYP3A4 inhibitor.
In the label
It says ” Because of a significant increase in exposure to siponimod, concomitant use of MAYZENT and drugs that cause moderate CYP2C9 and moderate or strong CYP3A4 inhibition is not recommended. This concomitant drug regimen can consist of a moderate CYP2C9/CYP3A4 dual inhibitor (e.g., fluconazole) or a moderate CYP2C9 inhibitor in combination with a separate – moderate or strong CYP3A4 inhibitor.
The and is underlined, does in mean avoid use of drugs that inhibit both CYP2C9 and CYP3A4 or CY2C9 or CYP3A4. As ritonavir is not an inhibitor of CY2C9, it is not an inhibitor of CYP2C9 and CYP3A4 and potentially would not be covered by the warning…..but as there is a warning about CYP2C9 and CYP3A4 inhibitors and siponimod, I suspect people will stay clear and use an alternative anti-viral treatment, despite the fact that the COVID-19 drug is only taken for 5 days, and higher siponimod doses have been tested and are relatively safe in humans.
Now I have questioned the significance of the AND with the Medical Liason Officiers, so I know the answer, but surely it is up to the manufacturers to make a call about their own compounds.
Why write this post….Well it is for you AND especially for some doctors, as it is is interesting to see which products they are recommending to the UK Government that they should be avoided if use of paxlovid is considered (NHSE advice 29 January 2022).
Disclaimer. This is the opinion of the author of this post and does not represent the views of any instituion. This should not be taken as medical advice.
Title: #MSCOVID2019. Interacting with your drugs
Sourced From: multiple-sclerosis-research.org/2022/02/mscovid2019-interacting-with-your-drugs/?utm_source=rss&utm_medium=rss&utm_campaign=mscovid2019-interacting-with-your-drugs
Published Date: Sat, 05 Feb 2022 13:00:00 +0000