A review of drug interactions with boceprevir and telaprevir: implications for HIV and transplant patients

Wilby, Kyle John; Greanya, Erica D.; Ford, Jo Ann E.; Yoshida, Eric M.; Partovi, Nilufar

doi:10.1016/s1665-2681(19)31022-1

Cited by 64 publications

(52 citation statements)

References 19 publications

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“…Nevertheless, the management of HIV-infected transplant recipients is complex because there are numerous pharmacokinetic interactions between certain antiretroviral agents and immunosuppressants (5,6). Specifically, tacrolimus tends to demonstrate a longer half-life and more unpredictable levels (6).…”

mentioning

confidence: 99%

HIV and Liver transplantation: The British Columbia Experience, 2004 to 2013

Tan-Tam

Liao

Montaner

et al. 2014

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Historically, HIV-positive individuals have not been considered to be candidates for liver transplantation due to the need for further immunosuppresion of these patients post-transplant, as well as other factors such as pharmacokinetic interactions between the necessary antiretroviral and immunosuppressant drugs. However, HIV-positive individuals with end-stage liver disease are now eligible for liver transplantation in British Columbia. The purpose of this study was to summarize the outcomes of HIV-positive individuals referred for liver transplanation in British Columbia.

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mentioning

confidence: 99%

HIV and Liver transplantation: The British Columbia Experience, 2004 to 2013

Tan-Tam

Liao

Montaner

et al. 2014

Canadian Journal of Infectious Diseases and Medical Microbiolog

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“…In addition to their clinical AE profiles, both boceprevir and telaprevir are substrates and significant inhibitors of cytochrome (CY) P450 3A (CYP3A), and are known (telaprevir) or inferred (boceprevir) to be substrates and inhibitors of the P-glycoprotein 1 (PgP) Introduction transporter [10]. As a result, both drugs are associated with a number of pharmacokinetic interactions with concomitant medications, and are contraindicated for use with CYP3A substrates, for which elevated systemic exposure is associated with an increased risk of serious AEs [8,9].…”

mentioning

confidence: 99%

Effect of the Coadministration of Daclatasvir on the Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinyl Estradiol and Norgestimate

et al. 2013

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Background: Daclatasvir is a highly selective NS5A replication complex inhibitor currently in development for the treatment of chronic hepatitis C infection. Daclatasvir is active at picomolar concentrations and demonstrates in vitro activity against a broad range of HCV genotypes. The primary objective of this study was to assess the effect of daclatasvir on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and norgestimate (Ortho Tri-Cyclen®). Methods: In this open-label single-sequence study, 20 healthy female subjects received ethinyl estradiol and norgestimate for three cycles, with coadministration of daclatasvir in cycle 3. Pharmacokinetics of ethinyl estradiol and the active metabolites of norgestimate (norelgestromin and norgestrel) were assessed in cycles 2 and 3. Results: Adjusted ratios of geometric means and 90% CIs were estimated for the maximum observed plasma concentration (ethinyl estradiol 1.11 [1.02, 1.20], norelgestromin 1.06 [0.99, 1.14] and norgestrel 1.07 [0.99, 1.16]) and area under the plasma concentration-time curve in one dosing interval (ethinyl estradiol 1.01 [0.95, 1.07], norelgestromin 1.12 [1.06, 1.17] and norgestrel 1.12 [1.02, 1.23]). Conclusions: Coadministration of daclatasvir resulted in no clinically relevant effects on exposure to ethinyl estradiol, norelgestromin or norgestrel.

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“…If this is confirmed in larger studies, only unique aspects for the management of HCV infection in persons with HIV coinfection may be needed to carefully consider the potential for drug interactions between the patient's antiretroviral drugs and the HCV direct-acting antiviral drugs (Table 2) [98][99][100]. For some patients' drug regimens, this may represent the combination of many unique antiviral drugs each with a different mechanism of action to inhibit HIV or HCV or to block antiviral drug metabolism through inhibition of the patient's cytochrome P450 pathways (e.g., ritonavir or cobicistat) [101,102].…”

Section: Challenges To the Use Of Direct-acting Antivirals In Hiv-infmentioning

confidence: 99%

Management of acute and chronic HCV infection in persons with HIV coinfection

Sulkowski

2014

Journal of Hepatology

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Due to shared routes of transmission, acute and chronic infection with hepatitis C virus is common among persons living with HIV infection in many regions of the world. In the era of effective antiretroviral therapy, acute HCV infection has been increasingly recognized in HIV-infected persons, particularly men who have sex with men, and liver disease, including hepatocellular carcinoma, has emerged as a leading cause of morbidity and mortality in those with chronic HCV infection, particularly older adults with long-standing coinfection. Over the past decade, the foundation for the management of acute and chronic HCV infection has been interferon alfa. However, due the high burden of treatment-related side effects and low likelihood of sustained virologic response, the impact of treatment with peginterferon/ribavirin on the burden of HCV disease in has been limited. However, the anticipated availability of safe, tolerable and highly efficacious interferon-free, oral HCV direct-acting antiviral combination therapies promise to dramatically change the management of acute and chronic HCV infection in HIV-infected persons. Preliminary data from studies of such oral DAA regimens in HIV/HCV coinfected patients suggest that coinfection with HIV will not impair HCV cure with these regimens. Indeed, in the coming era of high effective oral HCV DAA treatments, the only special feature concerning treatment of acute and chronic HCV infection in HIV-infected patients may be drug interactions between the antiretroviral drugs for HIV infection and direct-acting antiviral drugs for HCV infection.

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A review of drug interactions with boceprevir and telaprevir: implications for HIV and transplant patients

Cited by 64 publications

References 19 publications

HIV and Liver transplantation: The British Columbia Experience, 2004 to 2013

HIV and Liver transplantation: The British Columbia Experience, 2004 to 2013

Effect of the Coadministration of Daclatasvir on the Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinyl Estradiol and Norgestimate

Management of acute and chronic HCV infection in persons with HIV coinfection

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