Liverpool HEP Interactions

Do Not Coadminister

Tenofovir alafenamide

Emtricitabine/Tenofovir-DF (FTC/TDF, PrEP)

Summary:

Emtricitabine/tenofovir-DF contains tenofovir-DF and should not be administered with tenofovir alafenamide.

Description:

Vemlidy should not be co-administered with products containing tenofovir disoproxil fumarate.

Vemlidy Summary of Product Characteristics, Gilead Sciences Ltd, November 2023.

No Interaction Expected

Tenofovir alafenamide

Cocaine

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cocaine is metabolised by several pathways (CYP- and non-CYP-mediated), with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Description:

(See Summary)

No Interaction Expected

Tenofovir alafenamide

Diosmin

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diosmin is a naturally occurring flavonoid. Diosmin-containing products are available as dietary supplements or on prescription (in certain countries). Interaction studies suggest that diosmin may be a weak inhibitor of CYP3A4 and P-gp. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Description:

(See Summary)

No Interaction Expected

Tenofovir alafenamide

Dolutegravir

Summary:

Coadministration of dolutegravir (50 mg once daily) and tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (10/200/150/150 mg) had no significant effect on the pharmacokinetics of dolutegravir and tenofovir alafenamide. The recommended dose of tenofovir alafenamide is 25 mg once daily.

Description:

Coadministration of dolutegravir (50 mg, once daily) and tenofovir alafenamide (10 mg, single dose, as emtricitabine/tenofovir alafenamide fixed-dose combination tablet) was studied. Tenofovir alafenamide Cmax and AUC increased by 24% and 19%, respectively. Tenofovir Cmax and AUC increased by 10% and 25%, respectively. Dolutegravir Cmax, AUC, and Cmin increased by 15%, 2%, 5%, respectively. No dose adjustment of Vemlidy or dolutegravir is required.

Vemlidy Summary of Product Characteristics, Gilead Sciences Ltd, November 2023.

Coadministration of dolutegravir (50 mg once daily) with emtricitabine/tenofovir alafenamide (200/10 mg, once daily) was studied in 10 healthy volunteers in a crossover study. Tenofovir alafenamide AUC and Cmax increased by 17% and 24%, respectively. Tenofovir AUC and Cmax increased by 25% and 10%, respectively. Dolutegravir pharmacokinetic parameters were similar to historical controls.

Pharmacokinetics of tenofovir alafenamide when coadministered with other HIV antiretrovirals. Begley R, Das M, Zhong L, et al. J Acquir Immune Defic Syndr, 2018, 78(4): 465-472.

No Interaction Expected

Tenofovir alafenamide

Ecstasy (MDMA)

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. MDMA is metabolised mainly by CYP2D6. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Description:

(See Summary)

No Interaction Expected

Tenofovir alafenamide

Ivabradine

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ivabradine is metabolised by CYP3A4. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Description:

(See Summary)

No Interaction Expected

Tenofovir alafenamide

Pivmecillinam

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pivmecillinam is hydrolysed to mecillinam which is excreted primarily in the urine with some biliary excretion. Renal excretion of intact tenofovir alafenamide is a minor pathway as it is mainly eliminated following metabolism to tenofovir. This results in 90% lower systemic levels of tenofovir compared to tenofovir-DF so clinically significant interactions via this pathway are unlikely.

Description:

(See Summary)

No Interaction Expected

Tenofovir alafenamide

Black cohosh (Actaea racemosa)

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction Is unlikely. Black cohosh does not appear to be a potent modulator of human drug metabolism. Standardized black cohosh supplements, when taken at recommended doses, pose little risk for herb-drug interactions. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Description:

(See Summary)

No Interaction Expected

Tenofovir alafenamide

Amitriptyline

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Tenofovir alafenamide is metabolised to tenofovir (major metabolite) by carboxylesterase-1 and cathepsin A, with no CYP metabolism described.

Description:

(See Summary)

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