diarrhea and the absorption of oral target therapy - 1288737

Hi kempten,

I haven't seen anything specific on this subject, but in general diarrhea can affect absorption of some drugs. On the other hand, drugs such as Tarceva and Tagrisso tend to be absorbed pretty quickly (for example, Tarceva is 60% absorbed at administration, and both tend to reach peak absorption within a few hours). So unless the diarrhea is very frequent, I wouldn't think it's a significant problem. On the other hand, it's better for many reasons (e.g., dehydration) to keep the diarrhea under control, so I don't think you'd want to be too frugal with the Imodium.

That being said, if diarrhea is uncontrolled, it's typical to reduce the TKI dose, which would be similar in effect to any lessened bioavailability caused by reduced absorption.

JimC
Forum moderator

Hi Kempten,

I certainly agree with your first statement, that it's best all around to try to control the diarrhea. Although I don't know how much the ongoing diarrhea would affect drug absorption, there's no doubt that using it to reduce weight is a bad idea regardless of any change in the absorption rate. Cancer patients need to keep their health up in order to best tolerate the difficulties of cancer treatment.

JimC
Forum moderator

Kempten,

I agree with Jim that diarrhea induced weight-loss, especially for patients with cancer, can lead to serious complications. Prolonged diarrhea can definitely result in electrolyte changes (like sodium, potassium and others) which can cause secondary heart problems and others....in addition to feeling awful due to dehydration. I recommend controlling the diarrhea with loperamide (Immodium) or through the use of other medications like Lomotil or even tincture of opium in some severe cases.

The question about whether diarrhea can decrease the absorption, and subsequent effectiveness, of erlotinib is an excellent one. We know that erlotinib's absorption decreases as the acidity decreases because food increases the absorption of the drug and gastric reflux drugs like omeprazole (Prilosec) and others decrease the absorption of the drug. Diarrhea and other causes can increase the gut pH (Active acidophilus and other "active cultures" decrease the pH and can help with restoring normal gut flora and function), but the amount of drug absorption decrease would be related to several factors especially the severity of the diarrhea and where in the GI tract any inflammation was occurring. The only information that I could find was that erlotinib's absorption was not effected in the case of cystic fibrosis, which also causes alteration in secretions.

Long story short, I don't think we know exactly how much absorption is changed in the case of diarrhea and likely depends on several factors, but in the case of mild to moderate diarrhea likely will not change the extent of absorption to a significant degree. In the case of severe diarrhea requiring fluid administration and possibly hospital admission, this could be more of a problem.

Hope this is helpful, Best wishes,
Dr. Walko