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 |