CC6 Warnings are not enough – A case series of ritonavir induced Cushing’s Syndrome and adreno-cortical failure

Abstract

Background Ritonavir is a potent inhibitor of the cytochrome P450 3A4 enzyme used to boost other protease inhibitors in the management of HIV infection. The metabolism of fluorinated steroids (eg fluticasone, triamcinolone), used for asthma, hay fever and arthritis, is inhibited by ritonavir causing increased exposure to corticosteroid. Cases of ritonavir induced Cushing’s syndrome and subsequent adrenocortical suppression were first reported in 1999. Despite awareness of this interaction new cases continue to occur. Aim To identify and describe patients in our cohort with iatrogenic Cushing’s ± adrenocortical suppression, and to investigate whether there were missed opportunities for prevention. Methods Cases were identified from laboratory and pharmacy records between January 2010 and December 2015. Data was collected on demographics, steroid use, presentation and outcome. GP and referral letters were reviewed. Results 25 cases were identified. The steroids were prescribed in many different specialties, most commonly primary care and rheumatology, as well as being obtained OTC. Duration of steroid use ranged from a single dose to 3 injections over one year. The most common presentation was weight gain, facial swelling, fatigue and postural dizziness. Long-term sequelae included diabetes, osteoporosis and avascular necrosis as well as creating anxiety and mistrust of the medical profession. Synacthen tests were performed in the majority of cases. The duration of adrenal suppression varied from 1 month to >4 years. Clinic letters first carried a postscript warning re the interaction in 2007. Discussion Iatrogenic Cushings/adrenocortical suppression carries significant long-term morbidity. Innovative strategies to improve dissemination of information to healthcare professionals and patients are needed.