Thank you NATAP.org. DHCP letter that came out today (Feb 6th, 2012) regarding drug-drug interactions with Boceprevir and ritonovir-boosted PIs. In short. "Merck does not recommend the coadministration of VICTRELIS and ritonavir-boosted HIV protease inhibitors."
S. Sethu K. Reddy, MD Merck & Co., Inc.
Vice President PO Box 250
US Medical Affairs West Point, PA 19486-0250
February 6, 2012
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
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-naïve 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.
Sincerely,
S. Sethu K. Reddy, MD
Enclosure: Prescribing Information for VICTRELIS
- 3 -
Indications and Usage for VICTRELISTM (boceprevir)
VICTRELIS was approved by the US Food and Drug Administration (FDA) on May 13, 2011 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 previously untreated or who have failed previous interferon and ribavirin therapy.
The following points should be considered when initiating VICTRELIS for treatment of chronic HCV
infection:
• VICTRELIS must not be used as monotherapy and should only be used in combination with PR.
• VICTRELIS efficacy has not been studied in patients who have previously failed therapy with a treatment
regimen that includes VICTRELIS or other HCV NS3/4A protease inhibitors.
• VICTRELIS in combination with PR has not been studied in patients documented to be historical null
responders (<2-log10 HCV-RNA decline by Treatment Week 12) during prior therapy with PR. The clinical
studies included subjects who were poorly interferon responsive. Subjects with <0.5-log10 HCV-RNA
decline in viral load at Treatment Week 4 with PR alone are predicted to have a null response (<2-log10
viral load decline at Treatment Week 12) to PR therapy.
• Poorly interferon responsive patients who were treated with VICTRELIS in combination with PR have a
lower likelihood of achieving a sustained virologic response (SVR), and a higher rate of detection of
resistance-associated substitutions upon treatment failure, compared to patients with a greater response
to PR.
Selected Safety Information for VICTRELIS
All contraindications to PR also apply since VICTRELIS must be administered with PR.
Because ribavirin may cause birth defects and fetal death, VICTRELIS in combination with PR is
contraindicated in pregnant women and in men whose female partners are pregnant. Avoid pregnancy in
female patients and female partners of male patients. Patients must have a negative pregnancy test prior to
therapy; have monthly pregnancy tests; and use 2 or more forms of effective contraception, including
intrauterine devices and barrier methods, during treatment and for at least 6 months after treatment has
concluded. Systemic hormonal contraceptives may not be as effective in women while taking VICTRELIS
and concomitant ribavirin.
VICTRELIS is contraindicated in coadministration with drugs that are highly dependent on CYP3A4/5 for
clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening
events. VICTRELIS is also contraindicated in coadministration with potent CYP3A4/5 inducers, where
significantly reduced VICTRELIS plasma concentrations may be associated with reduced efficacy.
Drugs that are contraindicated with VICTRELIS include: alfuzosin, carbamazepine, phenobarbital,
phenytoin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John’s
Wort (hypericum perforatum), lovastatin, simvastatin, drosperinone, Revatio® (sildenafil) or Adcirca®
(tadalafil) (when used for the treatment of pulmonary arterial hypertension), pimozide, triazolam, and orally
administered midazolam.
- 4 -
Anemia and/or Neutropenia – The addition of VICTRELIS™ (boceprevir) to PR is associated with an
additional decrease in hemoglobin concentrations compared with PR alone and/or may result in worsening
of neutropenia associated with PR therapy alone. Dose reduction or discontinuation of peginterferon alfa
and/or ribavirin may be required. Dose reduction of VICTRELIS is not recommended. VICTRELIS must not
be administered in the absence of PR.
Complete blood count (with white blood cell differential counts) must be conducted in all patients prior to
initiating combination therapy with VICTRELIS. Complete blood counts should be obtained at Treatment
Weeks 4, 8, and 12, and should be monitored closely at other time points, as clinically appropriate.
The most commonly reported adverse reactions (>35%) in clinical trials in adult patients receiving the
combination of VICTRELIS with PR were: fatigue, anemia, nausea, headache, and dysgeusia. Of these
commonly reported adverse reactions, fatigue, anemia, nausea, and dysgeusia occurred at rates ≥5%
above the rates for PR alone in either clinical study. The incidence of these adverse reactions in previously
untreated subjects that were treated with combination therapy with VICTRELIS compared with PR alone
were: fatigue (58% vs 59%), anemia (50% vs 30%), nausea (46% vs 42%), and dysgeusia (35% vs 16%),
respectively. The incidence of these adverse reactions in previous treatment failure patients that were
treated with combination therapy with VICTRELIS compared with PR alone were: fatigue (55% vs 50%),
anemia (45% vs 20%), nausea (43% vs 38%), and dysgeusia (44% vs 11%), respectively.
VICTRELIS is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for
drug-drug interactions must be considered prior to and during therapy.
Subscribe to:
Post Comments (Atom)
Posts
No comments:
Post a Comment