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Table 3 Commonly encountered drug-drug interactions with mifepristone

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

Drug

Interactiona

Impacta

Recommended approacha

HMG-CoA reductase inhibitors

 Simvastatin

CYP3A4 metabolism

Increased serum concentration of statins, resulting in increased side effects

Contraindicated – switch to rosuvastatin or pravastatin

 Lovastatin

CYP3A4 metabolism

Contraindicated – switch to rosuvastatin or pravastatin

 Atorvastatin

CYP3A4 metabolism (lesser extent)

Switch to rosuvastatin or pravastatin OR lower dose (no more than 20 mg)

 Fluvastatin

CYP3A4 metabolism (lesser extent)

Switch to rosuvastatin or pravastatin OR lower dose (no more than 20 mg)

Opioids

 Hydrocodone/APAP

CYP3A4 metabolism

Increased serum concentrations of opioids, increasing side effects

Use lowest effective dose and monitor for side effects

 Oxycodone

 Tramadol

 Methadone

CYP3A4 metabolism and QT prolongation risk

Increased serum concentrations of methadone, increasing side effects, and risk of life-threatening QT prolongation

Use lowest effective dose and monitor for side effects and EKG changes regularly. Switch to alternative opioid if possible.

 Fentanyl

CYP3A4 metabolism

Increased serum concentrations of fentanyl, leading to serious, life-threatening respiratory depression

Contraindicated – switch to alternative opioid

Anticoagulants

 Warfarin

CYP2C9 metabolism (major) and CYP3A (minor)

Increased risk of bleeding and elevated INR

Increase frequency of INR monitoring. Use lowest effective dose (consider 50% reduction). Monitor after starting mifepristone and with dose titrations.

 Rivaroxaban

CYP3A4 metabolism

Increased risk of bleeding

Not recommended

 Apixaban

CYP3A4 metabolism (major) and CYP2C9 (minor)

Increased risk of bleeding

Reduce dose of apixaban per prescribing information [37]; monitor for bleeding events

Antibiotics

 Azithromycin

QT prolongationb

Risk of QT prolongation

Hold mifepristone temporarily while treating infection

 Ciprofloxacin

 Levofloxacin

 Moxifloxacin

 Sulfamethoxazole/Trimethoprim

Benzodiazepines

 Alprazolam

CYP3A4 metabolism

Increased serum concentrations of benzodiazepines, increasing side effects

Depending on indication, preferred agents would be lorazepam or oxazepam for anxiety and temazepam for sleep

 Clonazepam

 Diazepam

 Triazolam

 Flurazepam

Second generation (atypical) antipsychotics

 Quetiapine

CYP3A4 metabolism (major) and QT prolongationa

Increased serum concentrations of antipsychotic, increasing side effects and risk of QT prolongation

Reduce dose and monitor patient and EKG

 Risperidone

 Aripiprazole

 Lurasidone

CYP3A4 metabolism (major)

Increased serum concentrations, increasing side effects of lurasidone

Contraindicated with strong CYP3A inhibitors per prescribing information

Anticonvulsants

 Phenobarbital

Induce CYP3A4 metabolism (strong)

Decreased serum concentrations of mifepristone

Monitor for clinical endpoints and patient’s improvement. Monitor for changes in seizure activity.

 Phenytoin

 Carbamazepine

 Oxcarbazepine

Induces CYP3A4 (weak)

Miscellaneous

 Diltiazem

CYP3A4 metabolism

Increased serum concentrations of mifepristone, diltiazem, and verapamil

Limit doses of both drugs. Start mifepristone at low doses and perform small and careful dose escalations.

 Verapamil

 Repaglinide

CYP2C8/2C9

Increased serum concentrations of repaglinide, increasing side effects

Reduce dose or use smallest recommended dose. Monitor blood glucose levels more frequently, especially postprandial levels.

 Non-steroidal anti-inflammatory drugs (NSAIDs)

CYP2C8/2C9

Increased serum concentrations of NSAIDs, increasing side effects

Avoid if possible or use smallest recommended dose and monitor for side effects

  1. aApplies to all listed drugs in class unless otherwise noted. bFor other potential interactions with drugs that prolong the QT interval, check online resources, such as https://crediblemeds.org/index.php/drugsearch
  2. Abbreviations: APAP acetaminophen, CYP cytochrome P450, EKG electrocardiogram