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Cobicistat/darunavir/formoterol/fluticasone-propionate Suppression of hypothalamus pituitary adrenal axis and iatrogenic Cushing syndrome: case report

A 49-year-old man developed suppression of hypothalamus pituitary adrenal axis and iatrogenic Cushing’s syndrome following concomitant administration of formoterol/fluticasone propionate and cobicistat/darunavir [dosages and outcomes not stated; not all routes stated]. The man, who had a long standing HIV-1 infection, presented for a scheduled visit. He reported progressive muscle weakness leading to difficulty in walking, weight gain, abdominal distension, dysthymia, worsening of back pain and ankle oedema. His antiretroviral therapy consisted of cobicistat/darunavir along with emtricitabine/tenofovir that was started more than a year prior to the presentation. Five months prior to the presentation, he started receiving formoterol/fluticasone propionate inhaler for an exacerbation of his underlying COPD. At presentation, clinical examination showed an abdominal distension with red striae and moon facies with proximal muscle weakness, dorso-cervical fat accumulation, skin telangiectasis and bilateral ankle oedema. Blood tests showed elevation of liver enzymes and leucocytosis. Radiographic studies demonstrated multiple osteoporotic vertebral fractures. Hormone level studies showed low levels of serum cortisol, urinary free cortisol and ACTH. The findings were suggestive of suppression of hypothalamus pituitary adrenal axis and iatrogenic Cushing’s syndrome secondary to pharmacological interaction between fluticasone propionate and cobicistat. He was admitted. Iatrogenic Cushing’s syndrome was complicated by cholestatic hepatitis and development of vertebral fractures with spinal cord compression that required surgical intervention. He also had paraplegia. The man’s cobicistat/darunavir was switched to dolutegravir and dose of formoterol/fluticasone-propionate was gradually reduced and eventually replaced in order to prevent adrenal crisis. Due to paraplegia, he was sent to a neuro-rehabilitation clinic and lost to follow-up thereafter. Monge E, et al. Iatrogenic cushing syndrome due to drug interaction between inhaled fluticasone and cobicistat. Infezioni in Medicina 27: 445-448, No. 4, Dec 2019. Available from: URL: https://www.ncbi.nlm.nih.gov/pubmed/31846997

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Reactions 18 Jan 2020 No. 1787