Venclexta interacts with many meds, including OTC ones and those for AIHA

[SofiaDeo]

I am doing some research on medication interactions with Venclexta, and I noticed that it seems to interact with a lot of common medications, including acetaminophen, ibuprofen, common stomach upset medications like the proton pump inhibitors (omeprazole), steroids commonly used for AIHA (prednisone) plus a number of SSRI's used for depression.

The package insert states that the Venclexta dose should be decreased by at least 50% when taking another pg-p inhibitor, but my own personal experience showed that when adding another pg-p inhibitor to my stable Venclexta regimen (a statin, simvastatin), it was actually the second drug that we saw increased drug levels/effects of. My liver function is, and has stayed, normal. So however these meds interact in our liver, it seems it's not always as cut and dried as originally thought. This glycoprotein pg-p was only discovered in the early 1970's, so drugs using this mechanism of action are relatively new and whether they induce or inhibit other drugs is, IMO, not 100% ascertained. Because Venclexta was so "new" (compare to, say, aspirin), I chose to add the statin this way, instead of blindly following the "50% reduction rule." I knew, being a pharmacist, it can take years to determine in a drug-drug interaction which drugs' concentration may be affected. So I put it to the test, and for me personally, it seems reducing the statin dose by 50% got me the desired statin effect without cutting my Venclexta dose and risking CLL resistance. I will also add, we watched closely for increased Venclexta side effects like worsening neutropenia, thrombocytopenia, or anemia. In fact those cells are slowly creeping up towards normal. It was effects from too high a dose of the simvastatin that showed up in my bloodwork. Obviously, until a Venclexta blood level test is available, I can't say for sure I don't actually have a higher Venclexta level than I would without the simvastatin, but it's not enough to cause apparent adverse effects.

So I am putting this unlocked post out there to remind people to be cautious even when using OTC's while on Venclexta, and to discuss with their pharmacist/physician when considering adding or removing pg-p inhibitor drugs to their regimen, as well as "moderate CYP3A inhibitors", which the package insert also says necessitates a 50% Venclexta reduction. There are a lot of them out there, Rx as well as OTC.

[Newdawn Administrator]

I’ve never been told to refrain from taking or reducing paracetamol (acetaminophen) whilst taking Venetoclax. In fact it’s been the recommended method of pain control for me. According to Drugs.com, ‘No interactions were found between Tylenol and venetoclax. This does not necessarily mean no interactions exist. Always consult your healthcare provider.’

I’ve been quite clearly warned about taking anti-inflammatories whilst on Venetoclax however.

Newdawn

[SofiaDeo in reply to Newdawn]

Yes, and you are being monitored by docs. There are other considerations regarding what docs recommend; in arthritis, for example, patients with low serum proteins may not have highly protein bound drugs like naproxen recommended at all, or at standard doses. Any dose would likely be much lower. Especially if there are renal problems. Acetaminophen isn't highly protein bound, so it will be preferred, in addition to being studied extensively and potential side effects generally milder than NSAIDs. The "no interactions exist" in drugs.com means no one has documented/tested for any, it's a standard disclaimer. But it's still a possibility and I am just giving a "head's up" so people are aware and will consider p-gp inhibitors as well as CYP3A inhibitors when starting Venclexta, or new medications while on Venclexta.

For example, acetaminophen was tested against digoxin and increased digoxin absorption:

pubmed.ncbi.nlm.nih.gov/238...

So patients on digoxin will likely be monitored closely when starting acetaminophen therapy.

Since many drugs haven't been tested against Venclexta, people just need to be aware of the possibility and not take these meds without docs monitoring for interactions. Not everyone will have a serious interaction, but Murphy's Law says someone likely will!

[Seok in reply to SofiaDeo]

Hi SofiaDeo

I’m taking sulfasalazine and Celebrex for psoriatic arthritis; wonder if they interact with Venetoclax? Are they p-gp inhibitors or CYP3A inhibitors? Both ankle swellings and declining Hb are side effects of Venetoclax, which were worsened after I started taking sulfasalazine and Celebrex 🤔

Seok

[SofiaDeo in reply to Seok]

Neither of those are considered to be pg-p or CYP3A inhibitors. Since the mechanism of action of sulfasalazine is not 100% understood, and it affects stomach tissues, it theoretically may IMO have an effect on certain pg-p medications, since pg-p is found in intestinal tissues which (among other things) is one of the places pg-p affects other drug concentrations. This is just my opinion, and to my knowledge there is no data supporting my "educated guess." Pg-p, and the drugs affecting it, is so relatively new in the world of medicine, that there is no proven certainty regarding my guess.

From reading your profile, it appears you are also taking ibrutinib along with the Venclexta. It would seem more likely that it is the interaction between 2 known medications affecting Hb (Venclexta and ibrutinib) that is contributing to Hb decrease. As far as the ankle swelling.....some people are "more sensitive" to standard doses of medications, and this "sensitivity" can increase over time, which we definitely see in ibutinib use with regard to arrythmias. So it is POSSIBLE that it will be seen with Venclexta use over time. It is also possible that side effects will DECREASE over time. This also occurs with certain ibrutinib side effects, and may turn out to be the case with Venclexta. We just don't have the data yet to be able to statistically say "this percentage of patients will see X effect", nor can we say "X affect will worsen/improve over time."

And other health parameters (liver and kidney function, other disease states) also affect how medications act in our bodies. Again, I am just trying to make people aware that there are potential interactions with commonly used OTC as well as Rx medications, and for patients to be aware, since we don't have enough data. We get this data by patients being aware, and reporting any side effects/adverse effects to their docs and pharmacists/chemists.

[Flute117]

Yes, please be careful as there are many interactions not necessarily listed on the packet insert. I checked with my specialist before taking anything - vitamins, allergy meds, Tylenol, or any prescription meds - while on Venclexta.

[Katinlr]

Any thoughts on the suggestion that use of statins enhances Venetoclax efficacy? There are a number of articles suggesting this although I don't see anything recent. Here is one:science.org/doi/10.1126/sci...

[SofiaDeo in reply to Katinlr]

Structure-Activity Relationship (SAR) modeling indicated that simvastatin could be synergistic with Venclexta, and there is a study published that looked to see if there was a difference depending on the type of statin, hydrophilic versus lipophilic. The factor that study associated with this lower incidence of CLL was lipophilic statin use.

cebp.aacrjournals.org/conte...

There is a current clinical trial using a statin with Venclexta in the US recruiting, in California.

clinicaltrials.gov/ct2/resu...

The SAR modeling plus other articles and the California study (which I unfortunately can't join) are the reason I am taking low dose simvastatin for my cholesterol abnormalities.

For anyone interested in an "intro to SAR and how it's used to find new drugs":

pharmafactz.com/drug-design...

[Palmetto]

Dear Sofia do you have any thoughts on dropping severely neutrophils after getting Regen covid?The two drugs that make the combo drug?