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Boceprevir – PI Interaction: A “Dear Doctor” Letter We Didn’t Want To Get

Posted Feb 10 2012 6:45am

By now I’m sure that most of you ID folks out there have received the following letter from Merck , the makers of boceprevir:

URGENT — IMPORTANT DRUG WARNING: VICTRELIS (BOCEPREVIR)

The purpose of this communication is to inform you of recent pharmacokinetic study results evaluating drug interactions between VICTRELIS, an oral chronic hepatitis C virus (HCV) NS3/4A protease inhibitor, and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors … VICTRELIS reduced mean trough concentrations of ritonavir-boosted atazanavir, lopinavir, and darunavir by 49%, 43%, and 59%, respectively. Merck does not recommend the coadministration of VICTRELIS and ritonavir-boosted HIV protease inhibitors.

Boceprevir levels were also substantially lowered by lopinavir/r and darunavir/r.

Yes, we already knew that the telaprevir-boosted PI interactions were tricky. It’s basically atazanavir/ritonavir, no other options.

(Outside of the boosted PIs, you can use raltegravir or efavirenz with telaprevir, but the latter requires, 1125 mg three times/day, upping the cost by 50%. Gasp .)

The reason this “Dear Doctor” letter was so disappointing was that boceprevir was supposed to be easier in this regard. In this study presented at IDSA of peg/ribavirin + boceprevir for co-infected patients, all boosted PIs were allowed, only NNRTIs excluded. But that study was small (n=64), and in hindsight perhaps the slower-than-expected HCV RNA reduction had a pharmacokinetic explanation.

For now, the bottom line is that there really is no optimal HCV protease inhibitor for HIV/HCV co-infected patients, especially for those on a boosted PI.

And why careful assessment of those with HIV/HCV is critical, as many patients are stable enough to wait for the next wave of HCV drugs.

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