Drug Interactions between Dolutegravir and Artemether-Lumefantrine or Artesunate-Amodiaquine

Walimbwa, Stephen; Lamorde, Mohammed; Waitt, Catriona; Kaboggoza, Julian; Else, Laura; Byakika-Kibwika, Pauline; Amara, Alieu; Gini, J Rolant; Winterberg, Markus; Chiong, Justin; Tärning, Joel; Khoo, Saye

doi:10.1128/aac.01310-18

Cited by 19 publications

(13 citation statements)

References 13 publications

(19 reference statements)

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“…(13)(14)(15)(16)(17)(18) Dolutegravir-based ART is being rapidly adopted as first-line HIV treatment; Dolutegravir is an HIV-integrase inhibitor reported to have minimal effects on CYP3A4 and a study has shown that DTGbased ART did not alter lumefantrine exposure significantly. (19,20) Additionally, no information is available on whether malaria or HIV disease may affect lumefantrine pharmacokinetics.…”

Section: Main Text (4116 Words) Introductionmentioning

confidence: 99%

An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment

Francis

Barnes

Workman

et al. 2020

Antimicrob Agents Chemother

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Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from 10 studies with 6,100 lumefantrine concentrations from 793 nonpregnant adult participants (41% HIV-malaria-coinfected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantrine exposure increased 3.4-fold with coadministration of lopinavir-ritonavir-based antiretroviral therapy (ART), while it decreased by 47% with efavirenz-based ART and by 59% in the patients with rifampin-based antituberculosis treatment. Nevirapine- or dolutegravir-based ART and malaria or HIV infection were not associated with significant effects. Monte Carlo simulations showed that those on concomitant efavirenz or rifampin have 49% and 80% probability of day 7 concentrations <200 ng/ml, respectively, a threshold associated with an increased risk of treatment failure. The risk of achieving subtherapeutic concentrations increases with larger body weight. An extended 5-day and 6-day artemether-lumefantrine regimen is predicted to overcome these drug-drug interactions with efavirenz and rifampin, respectively.

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Section: Main Text (4116 Words) Introductionmentioning

confidence: 99%

An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment

Francis

Barnes

Workman

et al. 2020

Antimicrob Agents Chemother

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“…This situation was seen with the antiretroviral dolutegravir. Licensed in 2013, it was shown to reduce viral load far more rapidly than comparator regimens 52 , to have a more favourable drug-drug interaction profile 53,54 , to be suitable for co-formulation with other antiretrovirals and potentially to incur fewer adverse effects 55 . Botswana made an early decision to transition national policy to use dolutegravir-based regimens as first-line, knowing that pregnancies would occur.…”

Section: Should Pregnant Women Be Considered 'Special' or 'Vulnerable': Non-maleficencementioning

confidence: 99%

Ethical issues in therapeutic use and research in pregnant and breastfeeding women

Weld

Bailey

Waitt

2021

Brit J Clinical Pharma

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“…If geographical PG data were easily and widely available, population-physiologically-based PK modelling could classify the same co-administration as contraindicated in some areas while recommended or neutral in others. Indeed, the recent availability of dolutegravir in LMICs may overcome some of these issues, as preliminary data reported no relevant clinical reduction of its concentration with standard doses of commonly used antimalarial regimens (as shown in Figure 2) [50].…”

Section: Pk and Pg Opportunitiesmentioning

confidence: 99%

The Manifesto of Pharmacoenosis: Merging HIV Pharmacology into Pathocoenosis and Syndemics in Developing Countries

Trunfio

Scabini²,

Pinna³

et al. 2021

Microorganisms

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Pathocoenosis and syndemics theories have emerged in the last decades meeting the frequent need of better understanding interconnections and reciprocal influences that coexistent communicable and non-communicable diseases play in a specific population. Nevertheless, the attention to pharmacokinetic and pharmacodynamics interactions of co-administered drugs for co-present diseases is to date limitedly paid to alert against detrimental pharmacological combos. Low and middle-income countries are plagued by the highest burden of HIV, tuberculosis, malaria, and helminthiasis, and they are experiencing an alarming rise in non-communicable disorders. In these settings, co-infections and comorbidities are common, but no tailored prescribing nor clinical trials are used to assess and exploit existing opportunities for the simultaneous and potentially synergistic treatment of intertwined diseases. Pharmacoenosis is the set of interactions that take place within a host as well as within a population due to the compresence of two or more diseases and their respective treatments. This framework should pilot integrated health programmes and routine clinical practice to face drug–drug interaction issues, avoiding negative co-administrations but also exploiting potential favourable ones to make the best out of the worst situations; still, to date, guiding data on the latter possibility is limited. Therefore, in this narrative review, we have briefly described both detrimental and favourable physiopathological interactions between HIV and other common co-occurring pathologies (malaria, tuberculosis, helminths, and cardiovascular disorders), and we have presented examples of advantageous potential pharmacological interactions among the drugs prescribed for these diseases from a pharmacokinetics, pharmacodynamics, and pharmacogenetics standpoint.

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Drug Interactions between Dolutegravir and Artemether-Lumefantrine or Artesunate-Amodiaquine

Cited by 19 publications

References 13 publications

An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment

An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment

Ethical issues in therapeutic use and research in pregnant and breastfeeding women

The Manifesto of Pharmacoenosis: Merging HIV Pharmacology into Pathocoenosis and Syndemics in Developing Countries

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