Macrolides for cough - 1249499

double trouble
Posts:573

Hi. This question is probably for Dr. Walko. I have been seeing a pulmonary physician in the hopes of getting my coughing and sputum production treated. He has mentioned bronchiectasis, and wants to treat me with a low dose long term macrolide pending approval of my hepatologist.

I found the following article, which I thought was very informative, but it raised a question.
http://www.hindawi.com/journals/pm/2011/751982/

The question came up while reading 1.1.2 (3).

Immunomodulatory Effect
Chronic inflammation is characterized by the recruitment of neutrophils with the release of lysosomal enzymes and the generation of reactive oxygen compounds, resulting in tissue damage. Macrolides reduce the quantity of neutrophils in the inflammation site by decreasing molecular adhesion (E-selectin, ICAM-1), integrins (CD11b/CD18), cytokines involved with chemotaxis (IL-8, IL-6, IL4, IL5), and TNFα.
Macrolides modulate phagocytosis indirectly reducing neutrophil survival by accelerating their apoptosis. They suppress the secretion of epithelial-derived neutrophil survival factors, as GM-CSF (granulocyte-macrophage colony-stimulating factor).
Initially, macrolides improve the host’s defense through neutrophil stimulation, production of proinflammatory cytokines and mediators such as IL-1, IL-2, IL6, and GM-CSF, and production of nitric oxide in order to contain the infection [32]. However, continuous use attenuates chronic inflammation, through the suppression of inflammatory mediators (Il-8, eotaxin, TNFα and GM-CSF), thus limiting tissue damage [33].

Does that mean the macrolide would eventually lower my neutrophil count?

He also has mentioned “bronchorrhea” and thinks my process is consistent with BAC.

Thanks in advance for any discussion.
Debra

Edited to add: I will begin 250mg biaxin bid

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Reply # - October 25, 2012, 05:38 PM

dr walko
Posts: 102

Debra,

Generally, I think of the decrease in neutrophils as specific to the site of action (i.e. in the lungs) and not in bone marrow where the white cells are created and what is measured when a CBC is drawn. The drug can sometimes cause the white cell count to go down, but this is through a different mechanism of action (direct toxicity on the bone marrow) or correcting an infection. (Infection causes the white cell count to increase).

I'll let the docs comment as well.

Stay strong, Debra! Keeping you in my thoughts.

Dr. Walko

Reply # - October 27, 2012, 09:11 AM

double trouble
Posts: 573

Also, I think, for Dr. Walko:

This from the full prescribing information for Xalkori:

7.1 Drugs That May Increase Crizotinib Plasma Concentrations
Coadministration of crizotinib with strong CYP3A inhibitors increases crizotinib plasma concentrations [see
Clinical Pharmacology (12.3)]. Avoid concomitant use of strong CYP3A inhibitors, including but not limited to
atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir,
telithromycin, troleandomycin, and voriconazole. Avoid grapefruit or grapefruit juice which may also increase
plasma concentrations of crizotinib. Exercise caution with concomitant use of moderate CYP3A inhibitors.

Since I was recently found to harbor the ALK rearrangement, Xalkori may be a treatment option, which is great, however, the pulmonologist just put me on clarithromycin in the hope of reducing mucin production and preventing infection. The dose is one 250mg caplet daily PO.

Since clarithromycin, and it looks like other macrolides as well, may increase plasma concentration of Xalkori, can you think of a possible alternative that I could suggest. The clarithromycin is very hard on my stomach as well.

I might be confused about this, but I think that I am already at risk of having higher concentrations of drugs in my system due to liver disease, but I might be confused on that point.

Thank you for any response.
P.S. Dr. Walko... Randy's Pizza! Yum!

Debra

Reply # - October 27, 2012, 01:07 PM

catdander
Posts:

Debra, I've contacted Dr. Walko though she may be a little long in responding on a Saturday morning/early afternoon (which it was at the time ; ) ).

Just an FYI,
Janine

Reply # - October 27, 2012, 01:22 PM

dr walko
Posts: 102

Debra,

You are completely correct about this, I apologize for not putting together both story lines!

Clairthromycin would interact with crizotinib by increasing the drug concentrations of crizotinib and putting you at risk for more side effects. There are other drugs in the same class, like azithromycin, that would not interact though I would definitely ask your pulmonologist for another recommendation.

Regarding increased amounts of the drug from liver disease, this may not be the case....generally most of the liver has to be damaged before we really start to see metabolism pathways being significantly affected. The bilirubin values often tell us how well ye olde liver is still able break down drugs since this is a measure of conjugation, which is one of the breakdown pathways.

Enjoy your pizza!
Dr. Walko

Reply # - October 27, 2012, 02:00 PM

double trouble
Posts: 573

Thank you for a Saturday response. And, I wish I had a Randy's pizza... I was just commenting that the Durham chain, Randy's, makes great pizza. If you haven't already tried it, you should!

Again, thanks, and I will make sure we change the macrolide if I start Xalkori.

You're the greatest.
Debra

Reply # - October 28, 2012, 08:33 AM

dr walko
Posts: 102

No Debra, YOU and the many others who are living with cancer and showing that it's possible are the greatest! It's people like you who continue to give me inspiration that makes what I do each day very rewarding and hopeful.

Thank YOU!

And I will have to check out Randy's...Dr. Weiss and I are partial to a Chapel Hill place called "IP3".

Take care and stay strong,
Dr. Walko

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