Endocrine Abstracts

Background: Fluticasone is an inhaled steroid commonly used for asthma with low systemic bioavailability (~9%). We present a case of significant Iatrogenic Cushing’s syndrome when fluticasone was used simultaneously with antiretroviral therapy.

Case: 27-year-old man was diagnosed with HIV in 2021. His antiretroviral therapy was simplified to GENVOYA (elvitegravir/cobicistat/tenofovir/alafenamide/emtricitabine) at the same time as starting a new inhaler for his asthma (Relvar-fluticasone furoate/vilanterol). Two months later, he presented with profound tiredness, weight gain and bilateral hip pain. He was profoundly Cushingoid. Investigation confirmed significant adrenal insufficiency (9am cortisol <22 nmol/l) and his DEXA scan confirmed osteoporosis. MRI showed bilateral avascular necrosis of femoral heads and he is now awaiting bilateral hip replacements. An alternative antiretroviral regime (BIKTARVY -bictegravir/tenofovir alafenamide/emtricitabine) was prescribed. His inhaler was changed to beclomethasone and his hydrocortisone replacement was tailored based on cortisol day curves.

Discussion: Cobicistat is a CYP3A4 inhibitor (a pharmacokinetic ‘booster’), given in HIV to increase bioavailability of antiretroviral medications. Fluticasone (a synthetic inhaled glucocorticoid) is metabolised via the CYP3A4 pathway. Co-prescription results in significant increases in the bioavailability of fluticasone and exogenous systemic steroid exposure causing Cushing’s syndrome with concomitant adrenal suppression. The degree of Cushing’s was unnoticed and caused profound clinical sequalae including destructive bone disease with lifelong consequences. This significant drug-drug reaction was not highlighted on electronic system as antiretroviral medications are prescribed on alternate system.

Conclusion: 1. Patients on CYP3A4 inhibitors therapy, including anti-retroviral therapy, should avoid inhaled steroid fluticasone. Beclomethasone, less dependent on CYP3A4 for metabolism, should be the alternative.

2. Any additional medication prescribed for HIV patients should be checked with drug interaction database* or discussed with a specialist HIV pharmacist

3. Patients should be advised to consult their HIV team for any new medication prescribed.*(https://www.hiv-druginteractions.org/),