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Table 2 Suggested recommendations for the management of concomitant antihypertensive, anticoagulant, and antidiabetes medications during mifepristone treatment

From: Clinical management of patients with Cushing syndrome treated with mifepristone: consensus recommendations

Antihypertensives

 •If patient is hypertensive at baseline, normalize blood pressure prior to starting mifepristone

 •Recommend MR antagonist (spironolactone) as first-line antihypertensive agent after assessment of renal function (eGFR). Start spironolactone before mifepristone if the patient’s baseline characteristics include hypertension, low or low-normal potassium levels, and/or edema.

 •Use clinical discretion when adjusting other antihypertensive agents, with particular focus on antihypertensive agents (e.g., ACE inhibitors, ARBs, loop diuretics, thiazides) that can affect serum potassium levels and eGFR, particularly when up-titrating spironolactone

 •Be mindful of combination antihypertensive medications. Single agents may be preferable.

 •If the patient is receiving a calcium channel antagonist, note there may be drug-drug interactions between mifepristone and both diltiazem and verapamil. Dihydropyridines are associated with edema, which may be exacerbated by MR activation

Anticoagulants

Aspirin

 •Low-dose aspirin (81 mg) is acceptable with mifepristone. Do not use NSAIDs due to potential drug-drug interaction.

Thienopyridines

 •Dose changes not recommended

Direct oral anticoagulants (DOACS)

 •Among this class, apixaban would be preferred, although there is some potential for drug-drug interaction. Reduce dose per prescribing information [37] and monitor for bleeding events

 •Do not use rivaroxaban due to higher risk of drug-drug interaction

Warfarin

 •Check international normalized ratio (INR) before starting mifepristone

 •Recommend prophylactically reducing the dose of warfarin by 50% at start of mifepristone

 •Check INR within 48–72 h after starting mifepristone and recheck again after an additional 72 h

 •Check INR following any change in mifepristone dose (within 48–72 h) and recheck again after an additional 72 h

 •After follow-up monitoring and no additional changes to warfarin, have patient continue to monitor INR per anticoagulant clinic guidance

Antidiabetes medications

Insulin

 •Closely monitor patients for frequent dose adjustments during mifepristone initiation and titration

 •Educate patients to self-monitor glucose levels several times daily, and if possible, arrange for online glucose data sharing

 •Use extreme caution when treating patients with premixed insulins or concentrated insulins (e.g., U-500)

 •Expect a decrease in patient caloric intake with mifepristone (reduction in hyperphagia)

 •Consider proactive adjustment of insulin dose prior to starting mifepristone:

  – If patient is on basal insulin only, consider reducing dose by 10–20%

  – If patient is on basal/bolus insulin, consider reducing bolus insulin by 50% in addition to 10–20% reduction in basal insulin, particularly in patients with severe insulin resistance

Non-insulin agents

 •Consider stopping sulfonylureas and meglitinides or reducing dose by 50% prior to starting mifepristone because of hypoglycemia risk

 •There is a potential drug-drug interaction between mifepristone and repaglinide

 •Caution against initiating a GLP-1 agonist at same time as mifepristone due to gastrointestinal side effects

 •SGLT-2 inhibitors carry a risk of fungal infection (genital mycotic infection). Monitor patients for volume depletion.

  1. Abbreviations: ACE angiotensin-converting-enzyme, ARB angiotensin II receptor blocker, eGFR estimated glomerular filtration rate, GLP-1 glucagon-like peptide-1, INR international normalized ratio, MR mineralocorticoid receptor, NSAIDs nonsteroidal anti-inflammatory drugs, SGLT-2 sodium-glucose co-transporter-2