Liverpool HEP Interactions

Interaction Checker

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No Interaction Expected

Ledipasvir/Sofosbuvir

Midazolam (parenteral)

Summary:

Midazolam is metabolised by CYP3A4 but ledipasvir is only a weak inhibitor of intestinal CYP3A4 in vitro. Coadministration with a single dose of ledipasvir alone increased midazolam Cmax by 7% and decreased AUC by 1%. Coadministration with ledipasvir once daily decreased midazolam Cmax and AUC by 5% and 11%, respectively. These changes are not clinically relevant and no effect is expected on ledipasvir/sofosbuvir concentrations. No dose adjustment of ledipasvir/sofosbuvir or midazolam is required.

Description:

Coadministration of midazolam (2.5 mg, single dose) with ledipasvir (90 mg, single dose) was studied. Midazolam Cmax increased by 7% and AUC decreased by 1%. Coadministration with ledipasvir (90 mg, once daily) was also studied. Midazolam Cmax and AUC decreased by 5% and 11%. No effect is expected on sofosbuvir or GS-331007 exposure. No dose adjustment of ledipasvir/sofosbuvir or midazolam is required.

Harvoni Summary of Product Characteristics, Gilead Sciences Ltd, January 2021.

Based on drug interaction studies conducted with ledipasvir and/or sofosbuvir no clinically significant drug interactions have been either observed or are expected when ledipasvir/sofosbuvir is used with midazolam. Coadministration of midazolam (2.5 mg, single dose) with ledipasvir (90 mg, single dose) was studied in 30 subjects. Midazolam Cmax increased by 7% but AUC decreased by 1%.

Harvoni US Prescribing Information, Gilead Sciences Inc., March 2020.

Coadministration of ledipasvir (90 mg, single dose) with midazolam (2.5 mg, single dose) was studied in 30 healthy volunteers. Midazolam AUC decreased by 1% and Cmax increased by 7%. The authors conclude that ledipasvir/sofosbuvir may be coadministrated with CYP3A substrates.

Lack of an effect of ledipasvir on CYP3A activity in healthy volunteers. Au N, German P, Li Y, et al. 17th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, Washington DC, 2016, Poster P_47.

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