Cotellic With Turmeric And Black Pepper Interaction

Answer

Thanks for reaching out! There are actually quite a number of herbals that have the potential to interact with Cotellic based on how the drug is metabolized, so it is certainly important to talk to your doctor before making any changes to your medication regimen (including adding on supplements).

I wouldn't say any herb is contraindicated (i.e., absolutely do not use), but based on the fact that some theoretically could interact Cotellic, and the lack of data to provide insight into how clinically significant a given interaction may be, it is likely prudent to avoid certain ones. 

Why Some Herbals May Interact With Cotellic (Cobimetinib)

Cotellic (cobimetinib) is a medication used to treat certain types of melanoma. It works by inhibiting a protein called MEK, which is involved in the growth and spread of cancer cells.

Cotellic is metabolized in the liver by an enzyme called CYP3A4. CYP3A4 is an enzyme responsible for metabolizing a wide range of drugs, including Cotellic. In fact, CYP3A4 is the most abundant drug-metabolizing enzyme in the liver and is responsible for metabolizing approximately 50% of all drugs that are metabolized by the cytochrome P450 system.

When a substance inhibits or induces CYP3A4 activity, it can affect the metabolism and clearance of drugs that are substrates of this enzyme. This is the risk with Cotellic.

Some herbs have been shown to alter CYP3A4 activity, which could lead to increased or decreased levels of Cotellic in the body.

For example, grapefruit and grapefruit juice are well known to contain compounds that inhibit CYP3A4 and should be avoided while taking Cotellic (this is a good example of the well-known 'Statin-grapefruit' interaction). Inhibition could increase drug levels (due to a decrease in metabolism), which could increase side effects.

St. John's wort, a popular herbal supplement used for depression, has also been shown to induce CYP3A4 activity (induce means to potentiate in this regard), which could decrease the levels of Cotellic in the body and reduce its effectiveness.

Other examples of herbs that may inhibit CYP3A4, at least to some degree, include:

• Goldenseal (Hydrastis canadensis)
• Milk thistle (Silybum marianum)
• Echinacea (Echinacea purpurea)
• Ginger (Zingiber officinale)
• Licorice (Glycyrrhiza glabra)
• Ginkgo (Ginkgo biloba)
• Green tea (Camellia sinensis) 
  

What About Turmeric & Black Pepper?

While studies are far from conclusive, turmeric has been reported to inhibit CYP3A4 activity. This interaction is detailed on one of our drug-herbal interaction pages.

It is important to note that studies showing turmeric inhibition of CYP3A4 are mostly in vitro (i.e., lab) and animal studies. Human studies are lacking (although there are some published case reports documenting a possible interaction).

Additionally, the degree of CYP3A4 inhibition may vary depending on the dose and form of turmeric used, as well as individual variations in metabolism.

CYP3A4 inhibition is the same concern with black pepper (sometimes referred to as piperine), which is very often added to dietary supplements to improve absorption. It also has been reported to inhibit CYP3A4 (as detailed on our interaction page).

Additional Thoughts From The Pharmacist

It is challenging to give a definitive recommendation on whether or not turmeric and black pepper are safe with Cotellic.

We certainly know there is a theoretical interaction based on what we know about Cotellic metabolism, and how turmeric and black pepper could slow it down (via 3A4 inhibition). This has the potential to increase drug concentrations, increasing the risk of side effects.

However, there have not been any studies that have specifically evaluated these supplements with Cotellic, so the clinical significance of the potential interactions isn't known.

To be on the safe side, it may be prudent to not combine Cotellic with any other drug or herbal that may inhibit CYP3A4 to avoid the increased risk of side effects, which can be numerous with Cotellic.

The prescribing information for Cotellic does specifically say not to combine with CYP3A4 inhibitors:

Effect of Strong or Moderate CYP3A Inhibitors on Cobimetinib
Coadministration of COTELLIC with itraconazole (a strong CYP3A4 inhibitor) increased cobimetinib systemic exposure by 6.7-fold. Avoid concurrent use of COTELLIC and strong or moderate CYP3A inhibitors. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors including certain antibiotics (e.g., erythromycin, ciprofloxacin) is unavoidable for patients who are taking COTELLIC 60 mg, reduce COTELLIC dose to 20 mg.

Now, turmeric and black pepper likely wouldn't be considered strong CYP3A4 inhibitors, but the general point here is to avoid drugs that could inhibit CYP3A4.

At the very least, it is important to talk to your doctor before making any medication changes so you can be appropriately monitored.

Final Words

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