Clinical Pharmacokinetics of the Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor Doravirine: An Assessment of the Effect of Patient Characteristics and Drug–Drug Interactions

Khalilieh, Sauzanne; Yee, Ka Lai; Sánchez, Rosa I.; Stoch, S. Aubrey; Wenning, Larissa; Iwamoto, Marian

doi:10.1007/s40261-020-00934-2

Cited by 22 publications

(28 citation statements)

References 79 publications

(228 reference statements)

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“…On the contrary to ritonavir or cobicistat, some NNRTIs (i.e., nevirapine, efavirenz, etravirine) are moderate to potent inducers of cytochrome P450 enzymes, and could potentially reduce exposure, and thus efficacy, of certain chemotherapy drugs [113]. Rilpivirine and doravirine are second-generation NNRTIs that do not induce the P450 system limiting their potential for interactions with chemotherapy [114,115].…”

Section: Drug Interactions Between Cart and Chemotherapymentioning

confidence: 99%

Hodgkin Lymphoma in People Living with HIV

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et al. 2021

Cancers

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Despite widespread use of combined antiretroviral therapy (cART) and increased life expectancy in people living with HIV (PLWH), HIV-related lymphomas (HRL) remain a leading cause of cancer morbidity and mortality for PLWH, even in patients optimally treated with cART. While the incidence of aggressive forms of non-Hodgkin lymphoma decreased after the advent of cART, incidence of Hodgkin lymphoma (HL) has increased among PLWH in recent decades. The coinfection of Epstein–Barr virus plays a crucial role in the pathogenesis of HL in the HIV setting. Currently, PLWH with HRL, including HL, are treated similarly to HIV-negative patients and, importantly, the prognosis of HL in PLWH is approaching that of the general population. In this regard, effective cART during chemotherapy is strongly recommended since it has been shown to improve survival rates in all lymphoma subtypes, including HL. As a consequence, interdisciplinary collaboration between HIV specialists and hemato-oncologists for the management of potential drug–drug interactions and overlapping toxicities between antiretroviral and antineoplastic drugs is crucial for the optimal treatment of PLWH with HL. In this article the authors review and update the epidemiological, clinical and biological aspects of HL presenting in PLWH with special emphasis on advances in prognosis and the factors that have contributed to it.

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Section: Drug Interactions Between Cart and Chemotherapymentioning

confidence: 99%

Hodgkin Lymphoma in People Living with HIV

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“…The etiology of the minor increases seen is unknown and could be secondary to variability. Based on collective data from the doravirine clinical program, variations of up to threefold increases are not expected to significantly impact safety as doses of up to 1,200 mg have been generally well tolerated in clinical studies [ 30 ]. With respect to antiviral efficacy, only decreases in C 24h GMR would be expected to impact efficacy, and a decrease in C 24h was not observed in this study [ 17 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

A Phase 1 Study to Evaluate the Drug Interaction Between Islatravir (MK-8591) and Doravirine in Adults Without HIV

et al. 2021

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Background and Objectives Islatravir (MK-8591) is a novel nucleoside analogue in development for the treatment and prevention of HIV-1 infection. Doravirine is a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection. This study evaluated the pharmacokinetics, safety, and tolerability of islatravir and doravirine coadministration in a double-blind, placebo-controlled, randomized, fixed-sequence study. Methods Adult participants without HIV infection were administered oral doravirine 100 mg (n = 10) or placebo (n = 4) once daily (QD) for 5 days, immediately followed by oral islatravir 2.25 mg (n = 10) or placebo QD (n = 4) for 14 days; islatravir 2.25 mg and doravirine 100 mg QD, or placebo QD, were then coadministered for 5 days. Pharmacokinetic and safety data were collected. Results Doravirine geometric least-squares mean ratios (90% confidence intervals (CIs)) of (doravirine + islatravir)/doravirine for the area under the plasma drug concentration-time curve over 24 h (AUC 0-24h ), maximum plasma concentration (C max ), and plasma concentration at 24 h post-dose (C 24h ) were not meaningfully impacted. Islatravir geometric least-squares mean ratios (90% CI) of (islatravir + doravirine)/islatravir for AUC 0-24h and C max were both close to unity, 1.06 (1.01, 1.12) and 1.08 (0.91, 1.27), respectively. All study regimens were generally well tolerated. Conclusion These results indicate that coadministration of islatravir and doravirine had no clinically meaningful effect on the pharmacokinetics of either drug, and support further clinical investigation of islatravir in combination with doravirine for the treatment of HIV-1 infection.

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“…Coadministration of doravirine and CYP3A inhibitors, such as ritonavir and ketoconazole, may result in increased plasma concentrations of doravirine [21,22]. However, no dose adjustment is needed, as the increases are not considered to be clinically relevant.…”

Section: Nonnucleoside Reverse Transcriptase Inhibitorsmentioning

confidence: 99%

Pharmacokinetic interactions of modern antiretroviral therapy

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Boffito

2021

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Drug-drug interactions (DDIs) have been a clinical challenge in HIV medicine for over two decades. The newer antiretroviral drugs (ARTs) have significantly fewer DDIs than protease inhibitors and boosted integrase inhibitors (INSTIs). The lower propensity of such newer antiretrovirals (e.g. unboosted integrase inhibitors; doravirine) to cause DDIs, has been largely offset by the ageing cohort of patients with multiple comorbidities, who are taking multiple chronic medicines. Furthermore, the introduction of newly marketed drugs into clinical practice needs to be closely monitored, as the new drugs may be perpetrators of DDIs, leading to a potential change in the efficacy or toxicity of the coadministered antiretrovirals.

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Clinical Pharmacokinetics of the Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor Doravirine: An Assessment of the Effect of Patient Characteristics and Drug–Drug Interactions

Cited by 22 publications

References 79 publications

Hodgkin Lymphoma in People Living with HIV

Hodgkin Lymphoma in People Living with HIV

A Phase 1 Study to Evaluate the Drug Interaction Between Islatravir (MK-8591) and Doravirine in Adults Without HIV

Pharmacokinetic interactions of modern antiretroviral therapy

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