Reactions 1836, p169 - 2 Jan 2021 1

Betamethasone dipropionate/cobicistat/darunavir interaction XS

Cushing’s syndrome: case report

A 41-year-old woman developed Cushing’s syndrome following concomitant administration of betamethasone dipropionate and
cobicistat/darunavir [not all routes and duration of treatments to reaction onset not stated].
The woman was admitted due to a 6-week history of weight gain (15kg), abdominal perimeter, oedema to lower limbs,
oligomenone, asthenia and proximal weakness. She had a history of HIV infection since 2007 and recently had been receiving
monotherapy with cobicistat/darunavir 800/150mg every 24h with good immunologic and virologic control. On admission, physical
examination showed distal oedema with pitting at the malleolar level, rounded facial features, proximal muscle weakness of lower
limbs, significant abdominal distension without visible stretch marks and buffalo hump. Laboratory parameters were as follows: BP
150/100mm Hg, glucose 196 mg/dL, mild alteration of the liver profile and elevated levels of LDH, total cholesterol and ESR.
Hormonal determinations showed suppression of corticotropin and morning cortisol while free cortisol in the lower limit of normal.
A CT scan ruled out changes in adrenal glands. Based on these results, Cushing’s syndrome secondary to probable exogenous cause
was suspected. Anamnesis revealed that she had not received systemic corticosteroid therapies in previous months. However, she
had been applying topical betamethasone dipropionate skin solution 0.5 mg/g daily on hands and forearms for exanthema since last
2 months. As the clinical symptoms started 2 weeks after initiating betamethasone dipropionate, its interaction with cobicistat/
darunavir was suspected.
The woman’s betamethasone dipropionate was therefore discontinued. After 4 months, she showed improvement in weight, BP,
cholesterol levels and abdominal perimeter. However, suppressed ACTH levels persisted while morning cortisol and free cortisol
were below the normal limits. According to the Naranjo algorithm, a causality score of 7 points indicated probable relationship of
betamethasone dipropionate and cobicistat/darunavir with Cushing’s syndrome.
Rosales-Castillo A, et al. Cushing’s syndrome due to interaction between topical betamethasone dipropionate and darunavir/cobicistat. Medicina Clinica 155: 466-467, No. 10,
27 Nov 2020. Available from: URL: http://doi.org/10.1016/j.medcli.2019.07.014 [Spanish; summarised from a translation] 803524937

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