Table 2.

Cushing's syndrome drugs' characteristics and possible interaction with COVID-19 medications.

Drug	Mechanism formulation dose	Side effects	Possible interactions with covid-19 drugs
Drugs with central pituitary action
Pasireotide*	Multi-ligand somatostatin receptors agonist 0.3, 0.6, and 0.9 mg, subcutaneous Recommended dose: 0.6 mg bid Maximum dose: 0.9 mg bid	Hyperglycemia Gastrointestinal side effects Hypocortisolism QTc prolongation Hypokalemia Liver dysfunction	Hydroxychloquine and Chloroquine may be used with attention on hypokalemia. Hydroxychloquine, Chloroquine, Azithromycin, Lopinavir, and Ritonavir prolong the QTc interval.
Cabergoline*	D2 dopamine receptor agonist 0.5 mg, oral Dose: 0.5–7 mg weekly	Nausea Orthostatic hypotension Neurological and psychiatric symptoms Liver dysfunction	Azithromycin may be used with attention in patient with neurological and psychiatric symptoms and balance disorders. Azithromycin is ergot-derived; be careful in the association with other ergot derivatives like cabergoline. Lopinavir/Ritonavir plasmatic concentrations can increase in association with cabergoline.
Drugs with perypheral adrenal action
Metyrapone*	Steroidogenesis inhibitor Blocks 11 beta hydroxylase 250 mg, oral Initial dose: 250–1,000 mg that must be titrated in the first month To avoid hypoadrenalism, this could be combined with replacement therapy	Hepatotoxicity Hypertension Hypokalemia Gastrointestinal discomfort Dizziness Hirsutism in women Adrenal crisis Edema Pneumocystis Jirovecii infection	Paracetamol hepatotoxic effect may be potentiated Hydroxychloquine and Chloroquine may be used with attention on hypokalemia
Ketoconazole	Steroidogenesis inhibitor Blocks the 11 beta, 17 alpha, 18 hydroxylase (inhibits synthesis of cortisol and also aldosterone and androgens) 200 mg, oral Initial dose: 200–600 mg/day Maximum dose: 800–1,200 mg/day Refracted doses: 2–3 times a day	Hepatotoxicity Gastrointestinal side effects Rash Gynecomastia Hypogonadism Adrenal insufficiency Liver dysfunction	Hydroxychloquine and Chloroquine may be used with attention on hypokalemia Hydroxychloquine, Chloroquine, Azithromycin, Lopinavir, and Ritonavir prolong QTc interval Metabolized by CYP3A4 cytochrome: Azithromycin and Lopinavir/Ritonavir may increase Ketoconazole concentration; Tocilizumab may decrease Ketoconazole concentration It is a CYP3A4 inhibitor and it can increase Glucocorticoid and Lopinavir/Ritonavir concentration Interaction with antiviral drugs like Ritonavir and antibiotic like Clarithromycine
Mitotane	Steroidogenesis inhibitor Adrenolytic action 500 mg, oral Dose: 0.5–3 g, three times a day	Hepatotoxicity GI discomfort Neurological disorders Hypothyroidism Hypogonadism	It is a CYP3A4 inhibitor and it can increase Glucocorticoid and Lopinavir/Ritonavir concentration Must be suspended in case of shock or infection
Drug with action on glucocorticoid receptor
Mifepristone	Reversible blockade of glucocorticoid receptor In Italy, the prescription is limited to compassionate use 200 mg, oral Dose: 300–1,200 mg/day	Hypokalemia Worsening hypertension Adrenal crisis	Metabolized by CYP3A4 cytochrome: Azithromycin and Lopinavir/Ritonavir may increase Mifepristone concentration; Tocilizumab may decrease Mifepristone concentration Hydroxychloquine and Chloroquine may be used with attention on hypokalemia
Drug with citotoxic action
Temozolomide*	Cytotoxic second generation alkylating agent by DNA methylation induces apoptosis by accumulation of alkylated substances 5, 20, 100, 140, 180, and 250 mg, oral Administered in cycles	Embryotoxic, Teratogenic, and Genotoxic Severe myelosuppression Pneumocystis Jirovecii infection Gastrointestinal side effects Asthenia Anorexia	Tocilizumab may induce myelosuppression and immunodepression

^*Denotes the medications that have been prescribed in the case report.