Letter to physicians about the interactions of the drug Victrelis (boceprevir) with ritonavir-enhanced protease inhibitors for HIV
12.03.2012
The marketing authorisation holder for the drug Victrelis 200 mg hard capsules (boceprevir), Merck Sharp & Dohme d.o.o., in cooperation with the Agency for Medicinal Products and Medical Devices (HALMED) has sent a letter to physicians who prescribe Victrelis to inform them of new findings regarding interactions with ritonavir-enhanced protease inhibitors for HIV.
HALMED issued the marketing authorisation for the drug Victrelis 200 mg hard capsules (boceprevir) on 11 January 2012. Victrelis is currently not available on the market of the Republic of Croatia, however, a certain number of patients receive the drug via interventional import. Victrelis (boceprevir) is a protease inhibitor for the hepatitis C virus (HCV) that is taken perorally. Victrelis is intended for the treatment of chronic infection with the hepatitis C genotype 1 virus, in combination with peginterferon alfa and ribavirin in adult patients with compensatory liver disease who were not previously treated or did not have a successful response to prior treatment.
The test results for the interactions of boceprevir with ritonavir that were available at the time of issuance of the marketing authorisation for Victrelis did not indicate a significant interaction between these two drugs, and therefore boceprevir was not expected to have a significant impact on concentrations of ritonavir-enhanced HIV protease inhibitors. Namely, it is standard practice that HIV protease inhibitors (enzymes responsible for the final phase of maturation of the replicated HIV virus), such as atazanavir, darunavir, lopinavir and others, are given with ritonavir. Ritonavir inhibits the metabolism of the HIV protease inhibitor, which results in an increase in the plasma concentrations of these drugs when taken at lower doses, or less frequent dosing of the HIV protease inhibitor.
New results of interaction tests in healthy volunteers indicate a significant reduction in the concentration of ritonavir-enhanced darunavir, lopinavir and atazanavir during simultaneous application with boceprevir, though the reduction of the concentration of atazanavir is less pronounced than for darunavir and lopinavir. Furthermore, the boceprevir concentrations in blood were significantly lower when applied with ritonavir-enhanced darunavir or lopinavir, while a reduced exposure to boceprevir in simultaneous application with ritonavir-enhanced atazanavir was not reported.
The consequences of reduced drug levels in blood may mean their reduced efficacy in patients infected with HIV and HCV, particularly since many patients infected with HIV are also infected with the hepatitis C virus.
Recommendation for prescribing physicians:
- The simultaneous application of boceprevir with darunavir/ritonavir or lopinavir/ritonavir is not recommended.
- The simultaneous application of atazanavir/ritonavir with boceprevir resulted in a lower exposure to atazanavir, which can be associated with weaker efficacy and a loss of control in the treatment of HIV. If the simultaneous application of these drugs is considered essential, it may be considered on a case-by-case basis for patients with suppression of the HIV virus load and strains of HIV not suspected to be resistant to HIV therapy. Increased clinical and laboratory monitoring of the patient is justified.
Recommendation for patients:
- Patients treated for HIV and hepatitis C should discuss their current therapy with their doctor during their next regular visit
- Patients may not terminate drug therapy without consulting their physician.
- Patients should contact their physician or pharmacist for any additional questions.
The letter to physicians is available here (in Croatian).
The new information pertaining to the safe use of the drug Victrelis will be included in the Summary of Product Characteristics and the Instructions for Use, upon their approval in the European Union.
Further research on the said interactions in patients co-infected with HIV and HCV are ongoing. HALMED will continue to monitor the safe use of the drug Victrelis, and will inform the public of all new information in a timely manner.
We hereby remind all health care professionals that they are obliged to report every adverse reaction to medicinal products to HALMED (in Croatian). Patients developing an adverse reaction may also report the same directly to HALMED, with the recommendation that they consult their doctor or pharmacists regarding any adverse reactions they observe for consultations on the continuation of therapy.
