Liverpool HIV Interactions

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Potential Interaction

Darunavir/Cobicistat/ Emtricitabine/Tenofovir alafenamide (DRV/c/FTC/TAF)

Dexamethasone (low dose; 16 mg or less)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Dexamethasone is metabolized by CYP3A4. Darunavir/cobicistat may increase dexamethasone concentrations due to inhibition of CYP3A4. A dose reduction of the glucocorticoid may be necessary with monitoring for symptoms of hypercorticism. Dexamethasone is a weak CYP3A4 inducer at a low dose and is unlikely to have a clinically significant effect on darunavir/cobicistat. No interaction is expected with emtricitabine. Although dexamethasone induces intestinal P-glycoprotein, low dose dexamethasone is not expected to significantly reduce absorption of tenofovir alafenamide. Note, it is expected that the risk of Cushing’s syndrome is less likely to occur when using dexamethasone at a low dose and for a short treatment duration as compared to higher doses and long treatment duration. Note, it is expected that the risk of Cushing’s syndrome is less likely to occur when using dexamethasone at a low dose and for a short treatment duration as compared to higher doses and long treatment duration.

Description:

Based on theoretical considerations (systemic) dexamethasone is expected to decrease darunavir and/or cobicistat plasma concentrations (CYP3A induction). Systemic dexamethasone should be used with caution when combined with Symtuza.

Symtuza Summary of Product Characteristics, Janssen-Cilag Ltd, June 2023.

Co-administration is expected to increase dexamethasone concentrations, but decrease darunavir and cobicistat concentrations. Co-administration with systemic dexamethasone (that induces CYP3A) may result in loss of therapeutic effect and development of resistance to Symtuza. Consider alternative corticosteroids. Co-administration with corticosteroids (all routes of administration) of which exposures are significantly increased by strong CYP3A inhibitors can increase the risk for Cushing’s syndrome and adrenal suppression. Alternative corticosteroids including beclomethasone, prednisone, and prednisolone (for which PK and/ or PD are less affected by strong CYP3A inhibitors relative to other steroids) should be considered, particularly for long term use.

Symtuza US Prescribing Information, Janssen Products, March 2023.