Dolutegravir and Emtricitabine, rilpivirine, and tenofovir interaction

Dolutegravir and Emtricitabine, rilpivirine, and tenofovir: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Emtricitabine, rilpivirine, and tenofovir (COMPLERA) label · effective 2025-07-16

Major

COMPLERA is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral medications for treatment of HIV-1 infection is not recommended.

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Major

Not Recommended with Other Antiretroviral Medications Because COMPLERA is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended.

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Minor

Lactic Acidosis/Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including TDF and FTC, components of COMPLERA, alone or in combination with other antiretrovirals.

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Minor

Comprehensive information regarding potential drug-drug interactions with other antiretroviral medications is not provided.

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From the Dolutegravir (Tivicay) label · effective 2026-05-22

Moderate

…following drugs can be coadministered with dolutegravir without a dose adjustment: atazanavir/ritonavir, darunavir/ritonavir, elbasvir/grazoprevir, methadone, midazolam, omeprazole, oral contraceptives containing norgestimate and ethinyl estradiol, prednisone, rifabutin, rilpivirine, sofosbuvir/velpatasvir, and tenofovir [see Clinical Pharmacology ( 12.3 )] .

Drug interactionsnames Emtricitabine, rilpivirine, and tenofovirView label on DailyMed
Moderate

…dolutegravir exposures observed in INSTI-experienced patients (with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance [see Microbiology ( 12.4 )] ) upon coadministration with certain inducers may result in loss of therapeutic effect and development of resistance to TIVICAY or other coadministered antiretroviral agents.

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No interaction

However, in vivo, dolutegravir did not alter the plasma concentrations of tenofovir or para-amino hippurate, substrates of OAT1 and OAT3.

Drug interactionsnames Emtricitabine, rilpivirine, and tenofovirView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.