Flibanserin (Addyi) Drug Interactions

The FDA approved flibanserin for the treatment of acquired, generalized hypoactive sexual desire disorder in premenopausal women.  The drug was approved with a boxed warning and REMS (mandated monitoring) program due to the drug’s adverse effects profile.  Patients receiving flibanserin will need to be monitored closely for drugs they are currently receiving and drugs that may be added in the future.  Flibanserin will have a boxed warning regarding use with alcohol, liver disease and drugs that are moderate or strong inhibitors of CYP3A4 enzymes.  Much of the REMS program incudes mandatory education for physicians and pharmacists regarding the interaction between flibanserin and alcohol, but the long list of drugs that may potentiate the adverse effects with flibanserin warrants consideration in the drug’s use.  

Co-administration of flibanserin and CYP3A4 inducers may lead to a higher risk for very low blood pressure or loss of consciousness (syncope).  The CYP3A4 enzymes are the most prevalent CYP enzymes in the liver and involved in the metabolism of a large percentage of drugs.  A 1997 article estimated that CYP3A4 enzymes metabolized half of all drugs.  The macrolides, azole antifungals and protease inhibitors drug classes all have several drugs that inhibit CYP3A4.  Additional information will become available from popular references as more information is released.  Here are some common drugs that are strong inhibitors of CYP3A4 to consider:

• Antibiotics: clarithromycin, ciprofloxacin, erythromycin and telithromycin
  
• Antifungals: itraconazole, fluconazole, ketoconazole, posaconazole, miconazole and voriconazole
  
• Protease inhibitors: Amprenavir, fosamprenavir, atazanavir, darunavir, ritonavir, indinavir, lopinavir, nelfinavir, saquinavir, telaprevir
  
• Antidepressants: nefazodone 
• Calcium channel blockers: diltiazem and verapamil.
  
• Antiarrhythmics: Amiodarone 
  
• Hypernatremia treatment: Conivaptan
  
• Antiemetics: Aprepitant
  
• Cancer Chemotherapy: Imatinib
  
• Antivirals for Hepatitis C: Boceprevir
  
• Grapefruit juice: can be a moderate o strong inhibitor depending on concentration

References

FDA press release for flibanserin approval
FDA Drug Interaction Table
Hansten and Horn review of CYP3A4 interactions
Classification of the inhibition strength of some common CYP3A4 inhibitors