Exogenous steroid-induced hypoadrenalism in a person living with HIV caused by a drug–drug interaction between cobicistat and intrabursal triamcinolone

Makaram, Navnit S; Russell, Clark D; Roberts, Simon; Stevens, Jarrad; Macpherson, Gavin

doi:10.1136/bcr-2018-226912

Cited by 9 publications

(5 citation statements)

References 30 publications

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“…In the early AIDS epidemic, adrenal disorders in HIV-infected individuals were often a consequence of opportunistic infections, neoplasms, or concomitant systemic illness, the morbidity of which declined rapidly due to potent antiretroviral therapy. The possible explanation of darunavircontaining agents induced adrenal disorder identi ed in our study may be due to drug-drug interaction of pharmacokinetic boosters with exogenous glucocorticoids 32 . Glucocorticoids, including nasal, inhaled, intra-articular, or topical ocular preparations, were widely used in HIV patients for non-AIDS-related conditions that occur more frequently and at a younger age than in uninfected persons 33 .…”

Section: Discussionmentioning

confidence: 66%

Real-world Safety Profile of Darunavir and its Boosted Agents: An Analysis of FDA Adverse Event Reporting System Database

Tian¹,

Yao²,

et al. 2021

Preprint

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This current investigation was aimed to generate signals for adverse drug events of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All adverse event (AE) reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio(PRR), Bayesian confidence propagation neural network(BCPNN) were used to detect the risk signals. A suspicious signal was generated only if the results of the three algorithms were all positive. A total of 10756 AE reports were identified commonly observed in cardiovascular, endocrine, musculoskeletal, gastrointestinal, hepatobiliary, metabolic, and nutrition system. 40 suspicious signals were generated, and therein 20 signals were not included in the label. Severe high signals (i.e. progressive extraocular muscle paralysis, acute pancreatitis, exfoliative dermatitis, acquired lipodystrophy and mitochondrial toxicity) were identified. In pregnant women, umbilical cord abnormality, fetal growth restriction, low birth weight, stillbirth, premature rupture of membranes, premature birth and spontaneous abortion showed positive signals. Darunavir and its boosted agents induced AEs in various organs/tissues, and were shown to be associated with multiple adverse pregnancy conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.

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Section: Discussionmentioning

confidence: 66%

Real-world Safety Profile of Darunavir and its Boosted Agents: An Analysis of FDA Adverse Event Reporting System Database

Tian¹,

Yao²,

et al. 2021

Preprint

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show abstract

“…Adrenal suppression and dysfunction were found related to the use of darunavir-containing agents. The possible explanation may be due to drug-drug interaction of pharmacokinetic boosters with exogenous glucocorticoids 26 . Glucocorticoids, including non-systemic preparations, were widely used in HIV patients for non-AIDS-related conditions 27 .…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of safety profile for darunavir and its boosted agents using data mining in the FDA Adverse Event Reporting System database

Tian¹,

Yao²,

et al. 2021

Sci Rep

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This current investigation was aimed to generate signals for adverse events (AEs) of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All AE reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) were used to detect the risk signals. A suspicious signal was generated only if the results of the three algorithms were all positive. A total of 10,756 reports were identified commonly observed in hepatobiliary, endocrine, cardiovascular, musculoskeletal, gastrointestinal, metabolic, and nutrition system. 40 suspicious signals were generated, and therein 20 signals were not included in the label. Severe high signals (i.e. progressive extraocular muscle paralysis, acute pancreatitis, exfoliative dermatitis, acquired lipodystrophy and mitochondrial toxicity) were identified. In pregnant women, umbilical cord abnormality, fetal growth restriction, low birth weight, stillbirth, premature rupture of membranes, premature birth and spontaneous abortion showed positive signals. Darunavir and its boosted agents induced AEs in various organs/tissues, and were shown to be possibly associated with multiple adverse pregnant conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.

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“…An HIV-infected patient developed ICS with adrenal insufficiency following co-administration of elvitegravir/cobicistat ART and fluticasone nasal drops (15). Exogenous steroid-induced adrenal suppression caused by the drug interaction between intrabursal triamcinolone and cobicistat-boosted darunavir (16), and interlaminar triamcinolone injections while on the HIV medication Stribild (elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine), have also been reported (17). To our knowledge, there have not been any prior reports of Cushing syndrome associated with the concomitant use of epidural triamcinolone and Genvoya.…”

Section: Discussionmentioning

confidence: 99%

Iatrogenic Cushing Syndrome In An Hiv-Infected Patient Secondary to Concomitant Therapy With Genvoya and Epidural Triamcinolone

Mathias

Epstein

2020

AACE Clinical Case Reports

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Objective: We report the first known case of Cushing's syndrome and secondary adrenal insufficiency in a patient with concomitant use of epidural triamcinolone and Genvoya ® (elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg) for HIV. The prompt recognition of this drug-drug interaction is critical to avoid adverse outcomes when glucocorticoids are used with antiretroviral treatment containing Cobicistat, a potent CYP3A4 inhibitor. Methods: The patient was evaluated by determining morning serum cortisol concentrations, the serum cortisol response to Cosyntropin, and a urine synthetic glucocorticoid panel that is capable of measuring triamcinolone. We also employed the Naranjo Nomogram for Causality as well as a Drug Interaction Probability scale to assess medication-related adverse effects. Long term outcome was assessed by measuring morning serum cortisol and ACTH levels. Results: A 76-year-old female with HIV on Genvoya presented with fatigue, weight loss, and hyperglycemia. She had received multiple epidural triamcinolone injections for chronic back pain before her presentation. We hypothesized that the patient's presentation of Cushing's syndrome and adrenal insufficiency was caused by the inhibition of triamcinolone metabolism by cobicistat. The patient's antiretroviral therapy was changed to a regimen without cobicistat. She was started on maintenance hydrocortisone to prevent an adrenal crisis. A repeat urine glucocorticoid panel, within three days of the patient's HIV regimen being changed, showed a significant decrease in triamcinolone levels. Conclusion: It is essential to avoid drugs that include cobicistat when administering glucocorticoids that are metabolized via the CYP3A4 pathway due to the risk of developing Cushing's syndrome and secondary adrenal insufficiency.

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Exogenous steroid-induced hypoadrenalism in a person living with HIV caused by a drug–drug interaction between cobicistat and intrabursal triamcinolone

Cited by 9 publications

References 30 publications

Real-world Safety Profile of Darunavir and its Boosted Agents: An Analysis of FDA Adverse Event Reporting System Database

Real-world Safety Profile of Darunavir and its Boosted Agents: An Analysis of FDA Adverse Event Reporting System Database

Systematic analysis of safety profile for darunavir and its boosted agents using data mining in the FDA Adverse Event Reporting System database

Iatrogenic Cushing Syndrome In An Hiv-Infected Patient Secondary to Concomitant Therapy With Genvoya and Epidural Triamcinolone

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