SAT340 Matters Of The HAART - Ritonavir Induced CYP3A4 Inhibition of Intranasal Fluticasone Leading To Cushing’s Syndrome

Abstract

Abstract Disclosure: A. Ramachandran: None. S. Ghaith: None. A. Ramachandran: None. Background: Ritonavir, a potent inhibitor of the CYP3A4 enzyme, can lead to high systemic concentrations of even intranasal steroids causing Cushing’s syndrome. Case: A fifty-seven-year-old man with history of HIV on HAART presented with a 3-month history of fatigue, weight gain and easy bruising. History was negative for heat/cold intolerance, hair loss, constipation, erectile dysfunction. Medications included emtricitabine-tenofovir-alafenamide and ritonavir at stable doses for several years. He denied taking any oral or topical steroids, but reported using over the counter (OTC) fluticasone propionate (FP) for the past 6 months for seasonal allergies. Physical examination was significant for moon facies and abdominal striae. Labs were remarkable for low serum morning cortisol of 0.6 µg/dl (0.4-22.6 µg/dl), and low serum ACTH of <5 pg/ml (7-69 pg/ml). A diagnosis of exogenous steroid induced Cushing’s syndrome, as a result of ritonavir induced increase in FP levels was made. FP was gradually tapered and stopped. Serum cortisol and ACTH levels normalized at 15 µg/dl and 13 pg/ml respectively and his symptoms resolved completely after three months. Discussion: Ritonavir, a protease inhibitor (PI), is one of the strongest known inhibitors of CYP3A4 and is generally used to boost the plasma levels of other PIs. FP, a potent glucocorticoid, is generally used as monotherapy or as a combination inhaler in the treatment of asthma. It is rapidly metabolized by CYP3A4 and hence produces minimal side effects. However, its concurrent use with ritonavir results in increased serum concentration of FP leading to systemic adverse effects of glucocorticoids. Due to emerging awareness about this drug-drug interaction among physicians, prescription of inhalational steroids in patients on ritonavir is avoided. However, FP is an OTC intranasal glucocorticoid that is easily accessible, and its self-use is often times not reported by patients which makes it difficult for physicians to track on their patient’s medication list. A thorough review of OTC medications/supplements needs to be done when Cushing’s syndrome from exogenous steroids is suspected. It is also imperative that patients on ritonavir be counseled about the risks of taking any form of steroid formulations by any route. Conclusion: Educating patients on ritonavir about steroids being a component of many OTC medications/supplements, and a careful medication history and drug-drug interaction assessment is important in preventing steroid related adverse effects. Presentation: Saturday, June 17, 2023