Liverpool HIV Interactions

Cookies help us deliver our services. By using our services, you agree to our use of cookies. Learn more

Potential Interaction

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

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration of doravirine and multiple doses of the moderate CYP3A4 inducer rifabutin (300 mg once daily) decreased doravirine AUC, and Cmin by 50% and 68%, respectively. The product label for Delstrigo recommends to increase doravirine dosage to 100 mg twice daily when co-administered with rifabutin by taking an additional tablet of doravirine alone approximately 12 hours after the dose of Delstrigo. Lamivudine and tenofovir-DF are not impacted by rifabutin and therefore have to be maintained at the same dose (300 mg once daily). Doravirine should be kept at 100 mg twice daily for at least another 2 weeks following cessation of rifabutin due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.

Description:

If Delstrigo is co-administered with rifabutin, the doravirine dose should be increased to 100 mg twice daily. This is achieved by adding one 100 mg tablet of doravirine (as a single agent), to be taken approximately 12 hrs apart from the dose of Delstrigo. Coadministration of rifabutin (300 mg once daily) and doravirine (100 mg single dose) decreased doravirine AUC, Cmax and C24 by 50%, 1% and 68%, respectively.

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

Co-administration of doravirine (100 mg single dose) with rifabutin (300 mg once daily) was studied in 12 subjects. Doravirine AUC, Cmax and C24 decreased by 50%, 1% and 32% respectively. If Delstrigo is co-administered with rifabutin, take one tablet of Delstrigo once daily, followed by one tablet of doravirine 100 mg (Pifeltro) approximately 12 hours after the dose of Delstrigo for the duration of rifabutin co-administration. At least a 4-week cessation period is recommended prior to initiation of Delstrigo.

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

Co-administration of doravirine (100 mg, single dose) with rifabutin (300 mg, once daily, for 16 days) was studied in 12 healthy male subjects. Doravirine AUC, Cmax and C24 decreased by 50%, 1% and 68%, respectively. Pharmacokinetic modelling projected that doravirine (100 mg twice daily) and rifabutin (300 mg once daily) would result in similar steady-state Ctrough values as those observed with doravirine 100 mg once daily without rifabutin. Doravirine may be coadministered with rifabutin when the doravirine dose frequency is increased from 100 mg once daily to 100 mg twice daily.

Multiple doses of rifabutin reduce exposure of doravirine in healthy subjects. Khalilieh SG, Yee KL, Sanchez RI, et al. J Clin Pharmacol, 2018, (Epub ahead of print).

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