Combining Xtandi With Other Drugs

As a follow-up to my post on 4/12/13, I’m posting another question on Xtandi that appeared in Prostate Forum Volume 14 Number 10.

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What drugs or treatments are currently available to combine with Xtandi?

As this drug was only recently approved by the FDA, it will be a while before we see publications documenting the benefit or harm from Xtandi combinations. As a result, we can only talk about drug combinations where there are no known adverse drug interactions and where there is a theraputic rationale for the combination.
While Xtandi is currently approved for use after taxotere has failed, its characteristics make it attractive as part of initial treatment. There appear to be no apparent safety issues in combining Xtandi with the LHRH agonists Lupron, Zoladex, Trelstar or Eligard as part of initial treatment of poor prognosis widely metastatic prostate cancer. There are also no apparent safety issues in combining this drug with Firmagon in newly diagnosed patients where a very rapid response is needed.
Taxotere is cleared from the body in part via an enzyme called CYP3A4. This same pathway is used to some degree by Xtandi. Thus, there is a possibility that taxotere blood levels may be increased when the two are combined. Depending on the situation, the initial dose of one or both drugs may need to be reduced.
CYP3A4 is also used to clear ketoconazole and combining these two drugs would likely require major reduction in the initial doses of both drugs.
Carboplatin is often used in advanced prostate cancer. I can find no potential drug interactions between these two drugs.
At AIDP, we commonly use Leukine and have seen no adverse interactions between Leukine and Xtandi.
Zytiga and Xtandi share an interaction with CYP 3A4, but a clinical trial combining the two is currently in progress. I assume any drug interaction issues have been addressed. This combination has a strong biological rationale and I am very interested in the outcome of this trial.


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