Based on theoretical considerations darunavir/cobicistat is expected to increase triamcinolone plasma concentrations. (CYP3A inhibition). Concomitant use of darunavir/cobicistat and corticosteroids (all routes of administration) that are metabolised by CYP3A may increase the risk of development of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Co-administration with CYP3A-metabolised corticosteroids is not recommended unless the potential benefit to the patient outweighs the risk, in which case patients should be monitored for systemic corticosteroid effects. Alternative corticosteroids which are less dependent on CYP3A metabolism e.g. beclomethasone should be considered, particularly for long term use.

Coadministration is expected to decrease concentrations of darunavir and cobicistat and to increase concentrations of triamcinolone. Co-administration with systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to darunavir/cobicistat. 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.

A case study was reported of a 49-year-old HIV positive woman taking elvitegravir/cobicistat/tenofovir-DF/emtricitabine (Stribild: 150/150/300/200 mg, once daily) who developed severe lower back pain. After NSAID therapy failed to relieve the pain she received two interlaminar epidural injections of 80 mg triamcinolone. One month later she presented with moon facies, mild fatigue and weight gain. Tests revealed she had low ACTH and cortisol and indicated adrenal insufficiency. She continued on Stribild but was not administered further injections of triamcinolone. Follow up visits described eventual resolution of her moon facies and fatigue. The authors hypothesise a drug-drug interaction occurred via inhibition of CYP3A4 by cobicistat, leading to increased triamcinolone exposure and secondary adrenal insufficiency.