Thursday, February 9, 2012

Merck's Victrelis® (boceprevir) -- FDA Drug Safety Communication -- Drug Interaction

An anonymous commenter has very helpfully pointed us to a WSJ blurb -- but I've decided to run the entire FDA communication, since it involves issues of patient safety, and it is not uncommon to find Hep C co-infection in HIV-positive patient populations. Without additional introduction, then (more general FDA communication):

. . . .AUDIENCE: Infectious Disease, Pharmacy

ISSUE: FDA notified healthcare professionals and patients that drug interactions between the hepatitis C virus (HCV) protease inhibitor Victrelis® (boceprevir) and certain ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors (atazanavir, lopinavir, darunavir) can potentially reduce the effectiveness of these medicines when they are used together.

A drug interaction study showed that taking boceprevir (Victrelis) with ritonavir (Norvir) in combination with atazanavir (Reyataz) or darunavir (Prezista), or with Kaletra (lopinavir/ritonavir) reduced the blood levels of the HIV medicines and boceprevir in the body (see Data Summary below). FDA will be updating the Victrelis drug label to include information about these drug interactions.

BACKGROUND: Victrelis is a hepatitis C virus (HCV) protease inhibitor used with the medicines peginterferon alfa and ribavirin to treat chronic (long-lasting) hepatitis C infection in adults. HIV protease inhibitors are a class of anti-viral drugs used to treat HIV infection. Ritonavir is an HIV protease inhibitor used to “boost” other HIV protease inhibitors, increasing their levels in the blood and making them more effective.

RECOMMENDATION: Patients should not stop taking any of their medicines without talking to their healthcare professional. Patients should contact their healthcare professional if they have any questions or concerns.

Healthcare professionals who have started patients infected with both chronic HCV and HIV on Victrelis and antiretroviral therapy containing a ritonavir-boosted protease inhibitor should closely monitor patients for HCV treatment response and for potential HCV and HIV virologic rebound.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program. . . .

This will only widen the revenue/market-share gulf between Victrelis® and Incivek®, in my opinion, to Merck's material detriment.


Anonymous said...

It's been awhile since I was in a study support role but, as you pointed out, HepC and HIV are often co-infections. One would think this sort of data would have emerged as part of the concomitant meds module of the trial design.

In any event, your analysis is likely spot on - Merck will concede more market share. Another one of Fred's stars falls flat....

Anonymous said...

I am not familiar with the details of this program, but if HIV patients, or patients on antiretrovirals were excluded from the clinical trials (a common practice to exclude pts with significant co-morbidity) then it is possible this wouldn't emerge until now.

Anonymous said...

Point taken fellow Anon. I guess the latest development demonstrates the danger of excluding such subjects from study if they make up a broad group of the patient population.

Anonymous said...

I disagree, they knew and probably had the data in hand.

Merck and other companies plan these type of clinical studies all the time.

While not this compound, here is a ref: for a published paper by Merck for their CCR5 compound:

Short-term administration of the CCR5 antagonist vicriviroc to patients with HIV and HCV coinfection is safe and tolerable.
J Acquir Immune Defic Syndr. 2010 Jan;53(1):78-85

Anonymous said...

Thank you, Anon #3! I thought it incredibly odd the studies would have excluded co-infected HIV patients. It will be interesting to see what Merck/Legacy SP knew or didn't. The ultimate unfortunate position to be in is, of course, that of one of the Victrelis patients with HIV. Sad.