Liverpool HIV Interactions

Interaction Checker

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No Interaction Expected

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

Levonorgestrel (COC)

Quality of Evidence: Very Low

Summary:

Coadministration with Delstrigo has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Ethinylestradiol is mainly metabolized by hydroxylation. Coadministration of doravirine (100 mg once daily) and ethinylestradiol/levonorgestrel (0.03/0.15 mg once daily) did not significantly impair ethinylestradiol, levonorgestrel and doravirine exposures. Lamivudine and tenofovir-DF do not interact with levonorgestrel’s metabolic pathway.

Description:

Coadministration of ethinyl estradiol/levonorgestrel (0.03/0.15 mg single dose) and doravirine (100 mg once daily) decreased ethinyl estradiol AUC and Cmax by 2% and 17%; levonorgestrel AUC increased 21% and Cmax decreased by 4%. No dose adjustment is necessary.

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

No clinically significant change in ethinylestradiol or levonorgestrel concentrations were observed when co-administered with doravirine. No clinically significant drug interactions have been observed between TDF and oral contraceptives in studies with healthy subjects.

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

Co-administration of doravirine (100 mg, once daily, for 17 days) with ethinylestradiol/levonorgestrel (0.03/0.15 mg, single dose) was studied in 20 healthy female subjects. Ethinylestradiol AUC and Cmax were reduced by 2% and 17%, respectively, while levonorgestrel AUC was increased by 21% and Cmax decreased 4%. Changes to contraceptive pharmacokinetic parameters were not considered clinically relevant.

Effect of doravirine (MK-1439) on the pharmacokinetics of an oral contraceptive (ethinyl estradiol [EE] and levonorgestrel [LNG]. Anderson MS, Kaufman P, Castronuovo P, et al., 16th International Workshop on Clinical Pharmacology of Antiviral Therapy, Washington, May 2015, abstract: 60.

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