What is Addyi (flibanserin)?

What is Addyi (Flibanserin)?

Addyi (flibanserin) is an FDA-approved, non-hormonal prescription medication specifically indicated for treating acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women who have not previously experienced low sexual desire and whose low desire is troubling to them regardless of sexual activity type, situation, or partner. 1

FDA Approval and Indication

• Flibanserin received FDA approval in August 2015 for the treatment of HSDD in premenopausal women 2, 3
• It is NOT approved for use in postmenopausal women, men, or to enhance sexual performance 1
• The medication is not indicated for pediatric or geriatric patients 1

Mechanism of Action

• The exact mechanism by which flibanserin treats HSDD remains unclear 4, 1
• The drug acts as a multifunctional serotonin agonist/antagonist with high affinity for serotonin receptors: agonist activity at 5-HT1A and antagonist activity at 5-HT2A 1
• It is theorized to work by increasing dopamine and norepinephrine (responsible for sexual excitement) while decreasing serotonin (responsible for sexual inhibition) 5

Clinical Efficacy

• Flibanserin demonstrates modest efficacy, resulting in approximately 1 additional satisfying sexual event every 2 months compared to placebo 2, 4, 3
• The medication shows statistically significant improvements in sexual desire measured by the Female Sexual Function Index (FSFI) desire domain score 4
• Clinical trials demonstrated increases in the number of satisfying sexual events and sexual desire scores on validated measures while reducing distress related to female sexual dysfunction 6

Dosing and Administration

• The recommended dose is 100 mg taken once daily at bedtime only 1
• Taking flibanserin at any time other than bedtime increases the risk of low blood pressure, fainting, accidental injury, and excessive sleepiness 1
• Steady state is achieved after 3 days of dosing 1

Critical Safety Warnings (Boxed Warning)

Alcohol Interaction

• Do not drink alcohol close to the time of taking flibanserin 1
• After taking the bedtime dose, do not consume alcohol until the following day 1
• Combining flibanserin with alcohol significantly increases the risk of severe low blood pressure and fainting 1

Absolute Contraindications

• Any degree of hepatic impairment (flibanserin exposure increases 4.5-fold in patients with liver problems, dramatically increasing risks) 1
• Concurrent use with moderate or strong CYP3A4 inhibitors, including:
  • HIV protease inhibitors (ritonavir, atazanavir, indinavir, nelfinavir, saquinavir) 1
  • Oral antifungals (fluconazole, ketoconazole, itraconazole, posaconazole) 1
  • Certain antibiotics (ciprofloxacin, erythromycin, clarithromycin, telithromycin) 1
  • Hepatitis C medications (boceprevir, telaprevir) 1
  • Certain cardiac medications (diltiazem, verapamil) 1
  • Nefazodone (antidepressant) 1

Common Adverse Effects

• The most frequently reported side effects include dizziness, somnolence (sleepiness), nausea, and fatigue 6, 5
• Syncope (fainting) occurs rarely but is a serious concern, particularly in CYP2C19 poor metabolizers 1
• These adverse effects are typical of centrally acting drugs and are generally comparable to other CNS medications 6

Special Populations and Considerations

CYP2C19 Poor Metabolizers

• These patients have increased flibanserin exposure and require enhanced monitoring for adverse reactions, particularly hypotension 1
• CYP2C19 poor metabolizers represent approximately 2-5% of Caucasians and Africans, and 2-15% of Asians 1

Cancer Survivors

• Flibanserin has NOT been studied in women with a history of cancer or those on endocrine therapy 4
• The risk-benefit ratio in cancer survivor populations remains uncertain 4
• For premenopausal cancer survivors with HSDD, flibanserin is considered a reasonable option to discuss, along with alternatives like bupropion and buspirone 2

Pregnancy and Breastfeeding

• It is unknown if flibanserin harms an unborn baby 1
• Breastfeeding is not recommended during treatment with flibanserin due to potential for serious adverse reactions including sedation in breastfed infants 1

Clinical Context and Alternatives

• Before flibanserin's approval, HSDD was often managed with off-label therapies including bupropion, buspirone, and testosterone 2, 6
• These off-label options remain alternatives for patients who cannot take flibanserin or prefer other options 2, 7
• Bremelanotide is another FDA-approved medication for HSDD in premenopausal women, used as a self-administered subcutaneous injection as needed 7

Important Clinical Pitfalls

• Do not prescribe flibanserin to patients who drink alcohol regularly or cannot abstain from alcohol 1
• Always screen for liver disease before prescribing, as any hepatic impairment is an absolute contraindication 1
• Conduct a thorough medication reconciliation to identify contraindicated drug interactions before initiating therapy 1
• Set realistic expectations: the clinical benefit is modest (approximately one additional satisfying sexual event every two months) 2, 4
• Ensure patients understand that flibanserin must be taken daily at bedtime, not on an as-needed basis 1