Provided by HIVandHepatitis.com
Published on Tuesday, 07 February 2012 00:00
Written by Liz Highleyman
HIV/HCV coinfected people who take the HCV protease inhibitor boceprevir (Victrelis) for hepatitis C treatment along with a ritonavir-boosted HIV protease inhibitor may experience drug-drug interactions that reduce concentrations of both drugs to ineffective levels, Merck warned this week.
The approval this past May of the HCV protease inhibitors boceprevir and telaprevir (Incivek) have ushered in a new era of chronic hepatitis C treatment. Both drugs are approved only for HIV negative people, but studies in progress indicate that boceprevir and telaprevir -- when added to pegylated interferon plus ribavirin -- improve the likelihood of virological response for HIV/HCV coinfected people as well.
Despite the absence of completed trials, some clinicians are already prescribing the new HCV drugs off-label for coinfected patients due to their need for better treatment and the lack of other options. The new findings underscore advocates' insistence that interactions between HCV direct-acting antiviral agents and antiretroviral drugs and other medications commonly used by people with hepatitis C should be thoroughly evaluated early in the development process.
In the ongoing Phase 2b boceprevir coinfection trial, previously untreated HIV/HCV coinfected patients with HCV genotype 1 were randomly assigned to receive pegylated interferon/ribavirin with or without boceprevir. Participants were on optimized antiretroviral therapy with stable undetectable HIV viral load and CD4 counts of at least 200 cells/mm3. Based on prior drug-drug interaction data, they were limited to regimens containing a ritonavir-boosted protease inhibitor plus 2 selected nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).
The data released this week, however, show that boceprevir may reduce the mean trough (lowest) concentrations of ritonavir-boosted atazanavir (Reyataz), darunavir (Prezista), and lopinavir/ritonavir (Kaletra) by 40% to 60%. Darunavir/ritonavir and lopinavir/ritonavir also lowered boceprevir levels by 30% to 40%. These reductions are considered clinically significant, meaning they could lead to viral breakthrough and development of drug resistance.
Below is an edited excerpt from a "Dear Healthcare Provider" letter by Merck Vice President S. Sethu K. Reddy, MD, describing the drug-drug interactions and steps clinicians should take. Reddy emphasized that "Merck does not recommend the coadministration of Victrelis and ritonavir-boosted HIV protease inhibitors."
IMPORTANT DRUG WARNING
SUBJECT: Results of Pharmacokinetic Study in Healthy Volunteers Given Victrelis (boceprevir) and Ritonavir-Boosted HIV Protease Inhibitors May Indicate Clinically Significant Drug Interactions for Patients Coinfected with Chronic Hepatitis C and HIV
February 6, 2012
Dear Health Care Professional,
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 in healthy volunteers (n=39).
Victrelis is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection, in combination with peginterferon alfa and ribavirin (PR), in adult patients (18 years and older) with compensated liver disease, including cirrhosis, who are treatment-naive or who have failed previous interferon and ribavirin therapy. In the pharmacokinetic study, concomitant administration of Victrelis with Norvir (ritonavir) in combination with Reyataz (atazanavir) or Prezista (darunavir), or with Kaletra (lopinavir/ritonavir) resulted in reduced exposures of the HIV medicines and Victrelis.
Specifically, Victrelis reduced mean trough concentrations of ritonavir-boosted atazanavir, lopinavir, and darunavir by 49%, 43%, and 59%, respectively. Mean reductions of 34% to 44% and 25% to 36% were observed in AUC and Cmax of atazanavir, lopinavir, and darunavir. Coadministration of ritonavir-boosted atazanavir with Victrelis did not alter the exposure of Victrelis, but coadministration of Victrelis with lopinavir/ritonavir or ritonavir-boosted darunavir decreased the exposure of Victrelis by 45% and 32%, respectively.
These drug interactions may be clinically significant for patients infected with both chronic HCV and HIV by potentially reducing the effectiveness of these medicines when coadministered. Victrelis is not indicated for use in patients who are infected with both HIV-1 and chronic HCV. The safety and efficacy of Victrelis (boceprevir) has not been established in this coinfected population. Merck does not recommend the coadministration of Victrelis and ritonavir-boosted HIV protease inhibitors.
Health care providers who might have initiated Victrelis in combination with PR in HIV-HCV coinfected patients on fully suppressive antiretroviral therapy containing a ritonavir-boosted protease inhibitor should discuss these findings with those patients, and closely monitor those patients for HCV treatment response and for potential HCV and HIV virologic rebound.
Patients should be advised to contact their health care provider before stopping any of their medications.
Merck is sharing these pharmacokinetic data with regulatory authorities in the countries where Victrelis is approved. Merck will be submitting requests to regulators to update the product labeling with these data.
These data have been submitted for scientific presentation at an upcoming medical forum.
For more information, please consult the enclosed Prescribing Information for Victrelis.
The Prescribing Information can also be found at http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf.
Should you have any questions, require further information on product safety, or wish to report an adverse event with Victrelis, please contact Merck at 1-877-888-4231. Alternatively, an adverse event can be reported directly to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
S. Sethu K. Reddy, MD
SSK Reddy, Merck. Results of Pharmacokinetic Study in Healthy Volunteers Given Victrelis (boceprevir) and Ritonavir-Boosted HIV Protease Inhibitors May Indicate Clinically Significant Drug Interactions for Patients Coinfected with Chronic Hepatitis C and HIV. Dear Health Care Professional letter. February 6, 2012.