Liverpool HIV Interactions

No Interaction Expected

Doravirine/Lamivudine/ Tenofovir-DF (DOR/3TC/TDF)

Elbasvir/Grazoprevir

Quality of Evidence: Very Low

Summary:

Coadministration with Delstrigo has not been studied. Coadministration of doravirine (100 mg once daily) and elbasvir/grazoprevir (50/200 mg once daily) increased doravirine AUC, Cmax and Cmin by 56%, 41%, 61%, respectively. The increase in doravirine exposure is not considered to be clinically relevant. Elbasvir/grazoprevir exposure was not significantly altered by doravirine. No clinically relevant interaction is expected with lamivudine. The interaction between elbasvir/grazoprevir and tenofovir-DF was evaluated in clinical studies, and no dose adjustments are required. There was no clinically significant effect on tenofovir pharmacokinetics when administered with elbasvir (tenofovir AUC, Cmax, Ctrough increased by 34%, 47%, 29%), grazoprevir (tenofovir AUC, Cmax, Ctrough increased by 18%, 14%, 24%) or elbasvir/grazoprevir (tenofovir AUC, Cmax and Ctrough increased by 27%, 14% and ~20%). Tenofovir-DF had no clinically significant effect on elbasvir (AUC, Cmax, C24 decreased by 7%, 12%, 8%) or grazoprevir (AUC, Cmax, C24 decreased by 14%, 22%, 11%).

Description:

Coadministration of elbasvir/grazoprevir (50/200 mg once daily) and doravirine (100 mg once daily) increased doravirine AUC, Cmax and C24 by 56%, 41% and 61%, respectively. Elbasvir AUC, Cmax and C24 all decreased by 4%; grazoprevir AUC and Cmax increased by 7% and 22%, but C24 decreased by 10%. No dose adjustment is required.

Delstrigo Summary of Product Characteristics, Merck Sharp & Dohme Ltd, November 2018.

No clinically significant change in drug concentrations were observed when doravirine was co-administered with elbasvir and grazoprevir.

Delstrigo US Prescribing Information, Merck & Co Inc, August 2018.

Co-administration of doravirine (100 mg once daily) and elbasvir/grazoprevir (200/50 mg once daily) was studied in 12 healthy subjects. Doravirine AUC, Cmax and C24 increased by 56%, 41% and 61%, respectively. Elbasvir AUC, Cmax and C24 all decreased by 4%. Grazoprevir AUC and Cmax increased by 7% and 22%, while C24 decreased by 10%. The modest increases in doravirine exposure are not clinically meaningful based on the therapeutic profile of doravirine and coadministration of doravirine with elbasvir/grazoprevir was generally well tolerated.

Investigation of pharmacokinetic interactions between doravirine and elbasvir-grazoprevir and ledipasvir-sofosbuvir. Ankrom W, Sanchez RI, Yee KL, et al. Antimicrob Agents Chemother, 2019, 63(5):pii: e02491-18.

Coadministration of tenofovir disoproxil fumarate (300 mg once daily) and elbasvir alone (50 mg once daily, n=10), grazoprevir alone (200 mg once daily, n=12), or elbasvir/grazoprevir (50/100 mg once daily, n=13) was studied in HIV/HCV-negative subjects. Elbasvir AUC, Cmax and C24 all decreased by ~10%; grazoprevir AUC, Cmax and C24 decreased by ~10%, ~20% and ~10% respectively. Tenofovir AUC and Cmax and C24 increased by 34%, 47% and ~30% with elbasvir alone and by 18%, 14% and ~20% with grazoprevir alone; administration with elbasvir/grazoprevir increased tenofovir AUC, Cmax and C24 by 27%, 14% and ~20%, respectively. No dose adjustments for elbasvir/grazoprevir or tenofovir-DF are needed for coadministration in HCV/HIV-coinfected people.
Assessment of drug interaction potential between the hepatitis C virus direct-acting antiviral agents elbasvir/grazoprevir and the nucleotide analog reverse-transcriptase inhibitor tenofovir disoproxil fumarate. Feng HP, Guo Z, Caro L, et al. Clin Pharmacol Drug Dev, 2019, 8(7):962-970.

View all available interactions with Doravirine/Lamivudine/ Tenofovir-DF (DOR/3TC/TDF) by clicking here.