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Hepatitis – Drug-drug Interactions

Drug-drug Interactions

Use of antiretrovirals may be restricted or require special precautions in patients with hepatic impairment. In addition, significant drug-drug interactions may occur between anti-HCV agents, antiretrovirals and drugs used in patients requiring transplantation.1

Interactions between antiretrovirals and agents used to treat chronic HBV infection
Adefovir

  • Potential interactions, identified through studies or within the product label, may occur between adefovir and
    • delavirdine
    • saquinavir2
  • The interaction between adefovir and maraviroc or raltegravir has not been assessed2
  • There are no clinically significant interactions predicted between adefovir and other HIV protease inhibitors (PIs), nucleoside reverse-transcriptase inhibitors (NRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs), maraviroc or raltegravir2

Entecavir

  • The interactions between entecavir and maraviroc, raltegravir or rilpivirine have not been assessed2
  • No known clinically significant interactions have been predicted between entecavir and HIV PIs, NRTIs, NNRTIs, maraviroc or raltegravir, based on their metabolic profiles2

Lamivudine

  • Co-administration of lamivudine and emtricitabine is contraindicated2
  • There are no clinically significant interactions expected between lamivudine and other HIV PIs, NRTIs, NNRTIs, maraviroc or raltegravir2

Telbivudine

  • Interactions between telbivudine and NRTIs, HIV NNRTIs, HIV PIs, maraviroc and raltegravir have either not been assessed, or have been predicted based on metabolic profiles2

Tenofovir

  • Potential interactions may occur between tenofovir and
    • didanosine
    • HIV PIs (except nelfinavir and tipranavir)2
  • No clinically significant interactions are expected between tenofovir and other HIV NRTIs, NNRTIs, maraviroc, raltegravir, nelfinavir or tipranavir2

Interactions between antiretrovirals and agents used to treat chronic HCV infection

Pegylated interferon alfa

  • Co-administration with zidovudine is contraindicated2
  • There are potential interactions between pegylated interferon alfa and all NRTIs2
  • No clinically significant interactions are expected between pegylated interferon alfa and HIV PIs, NNRTIs, maraviroc or raltegravir2

Ribavirin

  • Co-administration of ribavirin with didanosine or zidovudine is contraindicated2
  • There are potential interactions between ribavirin and
    • atazanavir
    • emtricitabine
    • stavudine2
  • No clinically significant interactions are expected between ribavirin and HIV NNRTIs, HIV PIs (with the exception of atazanavir), maraviroc or raltegravir2

Direct-acting antivirals: telaprevir and boceprevir

  • Boceprevir and telaprevir are approved for the treatment of HCV genotype 1 infection in patients without HIV infection4
  • If used in liver transplant or HCV-HIV co-infected patients, telaprevir and boceprevir should be administered with caution and under close clinical monitoring1
  • Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents from the US Department of Health and Human Services (DHHS), updated in March 2012, provide a comprehensive summary of considerations for the use of boceprevir or telaprevir and ART4
  • Due to drug-drug interactions and limited drug-interaction studies, telaprevir can only be safely combined with boosted atazanavir or efavirenz in combination with tenofovir or abacavir and emtricitabine or lamivudine3
    • with efavirenz, telaprevir doses need to be increased to 1125 mg every 8 hours3,4
    • data in combination with raltegravir will be published shortly, please check the viral hepatitis drug interactions website3
  • Boceprevir is not indicated for use in patients who are co-infected with HIV and chronic HCV4,5
    • interactions between boceprevir and ritonavir-boosted HIV PIs may be clinically significant for PLWHIV infected with chronic HCV by potentially reducing the effectiveness of these medicines when co-administered
    • coadministration of boceprevir with ritonavir-boosted HIV PIs or efavirenz is not recommended4,5
  • There are potential interactions between telaprevir or boceprevir and all HIV PIs, all HIV NNRTIs, zidovudine and maraviroc
    • in addition, there are potential interactions between telaprevir and abacavir or tenofovir2

Telaprevir and boceprevir have no known clinically significant interactions with raltegravir, didanosine, emtricitabine, lamivudine or stavudine.2

For a review of drug-drug interactions with boceprevir and telaprevir and antiretrovirals, access this review: A review of drug interactions with boceprevir and telaprevir: implications for HIV and transplant patients.6

For more information, access the viral hepatitis drug interactions website or the HIV drug interactions website.

References

  1. MG Ghany, DR Nelson, DB Strader, DL Thomas, and LB Seeff. AASLD Practice Guideline. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases.  Hepatology 2011;54:1433–1444.
  2. University of Liverpool. The Hepatitis drug interactions website. Accessed 5 March 2012.
  3. European AIDS Clinical Society (EACS). Guidelines Version 6.0. Accessed 30 November 2011.
  4. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-infected Adults and Adolescents. Department of Health and Human Services. Accessed 14 June 2012.
  5. Merck & Co Inc. Letter to Health Care Professional February 6 2012. 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. Accessed 2 March 2012.
  6. Wilby KJ, Greanya ED, Ford JA, et al. A review of drug interactions with boceprevir and telaprevir: implications for HIV and transplant patients. Ann Hepatol 2012;11:179–185.