Clinical Pharmacodynamics, Pharmacokinetics, and Drug Interaction Profile of Doravirine

Boyle, Alison; Moss, Catherine E.; Marzolini, Catia; Khoo, Saye

doi:10.1007/s40262-019-00806-9

Cited by 32 publications

(19 citation statements)

References 37 publications

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“…The broad suitability of doravirine in the presence of concomitant medications therefore offers freedom from some of the restrictions associated with other antiretroviral regimens and provides additional flexibility in managing polypharmacy. Similar conclusions have been drawn by other authors [106,107].…”

Section: Clinical Perspectivesupporting

confidence: 92%

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

et al. 2020

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Doravirine (MK-1439) is a novel non-nucleoside reverse transcriptase inhibitor indicated for the combination treatment of human immunodeficiency virus type-1 (HIV-1) infection. The recommended dose is 100 mg once daily. This review summarizes the pharmacokinetics of doravirine, the influence of intrinsic factors, and its drug-drug interaction (DDI) profile. Following oral administration, doravirine is rapidly absorbed (median time to maximum plasma concentration, 1-4 h) and undergoes cytochrome P450 (CYP)3A-mediated oxidative metabolism. Steady-state geometric means for AUC 0-24 , C 24 , and C max in individuals with HIV-1 following administration of doravirine 100 mg once daily are 37.8 μM•h, 930 nM, and 2260 nM, respectively. Age, gender, severe renal impairment, and moderate hepatic impairment have no clinically meaningful effect on doravirine pharmacokinetics, and there is limited potential for DDIs. No dose adjustment is necessary when doravirine is co-administered with strong CYP3A inhibitors. However, doravirine is contraindicated with strong CYP3A inducers (e.g., rifampin), and dose adjustment of doravirine is recommended for co-administration with the moderate CYP3A inducer, rifabutin. Included in this review are clinical trial data from phase I pharmacokinetic trials, including DDI trials and trials in participants with renal and hepatic disease but without HIV-1 infection (N = 326), as well as phase I, II, and III safety and efficacy trials in participants living with HIV-1 (N = 991). Based on these data, the pharmacokinetic profile of doravirine supports its use in diverse populations living with HIV-1 and allows co-administration with various antiretroviral agents and treatments for commonly occurring co-morbidities.

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Section: Clinical Perspectivesupporting

confidence: 92%

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

et al. 2020

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“…An excellent review performed by Boyle and colleagues addresses the general pharmacodynamic, pharmacokinetic, and drug interaction profile of doravirine. 23 Since its publication in August 2019, a phase one study evaluated oral granules as an alternative formulation for the single tablet of combination doravirine/tenofovir disoproxil fumarate/ lamivudine. Equivalence of each component administered was evaluated as granules as compared to their tablet equivalent when taken alone and in combination with either apple sauce or vanilla pudding.…”

Section: Pharmacokinetic/pharmacodynamicmentioning

confidence: 99%

<p>Doravirine and Its Potential in the Treatment of HIV: An Evidence-Based Review of the Emerging Data</p>

Rock

Lerner

Badowski

2020

HIV

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The utility of doravirine in the management of HIV-1 infection is approved for use in patients who are antiretroviral-naïve as well as patients who have achieved stable virologic suppression and are interested in replacing their current antiretroviral therapy. The role of doravirine continues to evolve as data emerges on the potential for new combination therapy with the investigational agent, islatravir, as well as a potential strategy to minimize post-marketing safety concerns with recommended first-line agents, such as integrase inhibitors. The goal of this review is to assess recent and emerging data on the non-nucleoside reverse transcriptase inhibitor, doravirine.

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“…Use of carbamazepine, phenytoin, oxcarbazepine is not recommended with doravirine as the mentioned AEDs will induce the metabolism of doravirine through up regulation of UGT1A1 and CYP 3A, so it is suggested to use alternative AEDs (Boyle et al, 2019).…”

Section: Potential Mechanism Of Drug To Drug Interactions Related To Co-administration Of Arvs and Aedsmentioning

confidence: 99%

Drug – Drug Interactions Between Newer Anti- Retroviral Drugs And Anti Epileptics - A Review

Vaishnavi

Balaji

Ramesh

et al. 2020

ijrps

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Drug – Drug Interactions (DDIs) are the leading cause of drug toxicity and emergence of drug resistance, ultimately leading to increased burden in People Living with Human Immunodeficiency Virus (PLHIV). On an average 55 % of people on Anti Retroviral Therapy (ARVs) are co-administered with Anti Epileptic Drugs (AEDs). The introduction of newer anti-retroviral drugs such as dolutegravir, bictegravir, emtricitabine, doravirine are proven to have less side effects, high tolerability and effective decrease in the viral load, but the risk of DDIs still stands to be high. This review briefly describes about the pharmacokinetic properties of dolutegravir, bictegravir, emtricitabine, doravirine, mechanism of interaction between the above mentioned ARVs and AEDs, effect of DDIs on ARVs, effect of DDIs on interacting AEDs, outcome of DDIs and possible management of DDIs. The pharmacokinetic type of DDIs was observed between the ARVs and AEDs. The majority of DDIs were found affecting the metabolism and the absorption of the drugs. UGT1A1, CYP 3A are the two important classes of metabolic enzymes involved in the DDIs and p- glycoprotein (P-gp) is the transporter involved in the DDIs affecting the absorption. Significant interactions have been found in between the above mentioned newer ARV’s with carbamazepine, oxcarbazepine, phenytoin and phenobarbitol.

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Clinical Pharmacodynamics, Pharmacokinetics, and Drug Interaction Profile of Doravirine

Cited by 32 publications

References 37 publications

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

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

<p>Doravirine and Its Potential in the Treatment of HIV: An Evidence-Based Review of the Emerging Data</p>

Drug – Drug Interactions Between Newer Anti- Retroviral Drugs And Anti Epileptics - A Review

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