Dosing and uses of Addyi (flibanserin)
Adult dosage forms and strengths
tablet
- 100mg
Hypoactive Sexual Desire Disorder
Indicated for premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not caused by a coexisting medical or psychiatric condition, problems within the relationship, or the effects of a medication or other drug substance
100 mg PO once daily at bedtime
Dosed at bedtime because administration during waking hours increases risks of hypotension, syncope, accidental injury, and CNS depression
Discontinued after 8 weeks if no improvement
Missed dose
- If a dose is missed at bedtime, instruct the patient to take the next dose at bedtime on the next day
- Instruct the patient to not double the next dose
CYP3A4 inhibitors
- Coadministration with moderate or strong CYP3A4 inhibitors is contraindicated
- If initiating flibanserin following moderate or strong CYP3A4 inhibitor use, start flibanserin 2 weeks after the last dose of the CYP3A4 inhibitor
- If initiating a moderate or strong CYP3A4 inhibitor following flibanserin use, start the moderate or strong CYP3A4 inhibitor 2 days after the last dose of flibanserin
Dosing Considerations
Acquired HSDD refers to HSDD that develops in a patient who previously had no problems with sexual desire
Generalized HSDD refers to HSDD that occurs regardless of the type of stimulation, situation, or partner
Limitations of use
- Not indicated for HSDD in postmenopausal women or in men
- Not indicated to enhance sexual performance
Pediatric dosage forms and strengths
Not indicated
Addyi (flibanserin) adverse (side) effects
>10%
Dizziness (11.4%)
Somnolence (11.2%)
Nausea (10.4%)
1-10%
Fatigue (9.2%)
Insomnia (4.9%)
Dry mouth (2.4%)
Anxiety (1.8%)
Constipation (1.6%)
Abdominal pain (1.5%)
Metrorrhagia (1.4%)
Rash (1.3%)
Sedation (1.3%)
Vertigo (1%)
Warnings
Black box warnings
Contraindicated with alcohoL
- Use with alcohol increases risk of severe hypotension and syncope; therefore, alcohol use is contraindicated
- Before prescribing flibanserin, assess the likelihood of the patient abstaining from alcohol, taking into account the patient’s current and past drinking behavior, and other pertinent social and medical history
- Counsel patients who are prescribed flibanserin about the importance of abstaining from alcohol use
- Because of the increased risk of hypotension and syncope is due to an interaction with alcohol, flibanserin is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ADDYI REMS Program
Contraindicated with moderate or strong CYP3A4 inhibitors
- Coadministration with moderate or strong CYP3A4 inhibitors increases flibanserin concentrations, which can cause severe hypotension and syncope
- Therefore, the use of moderate or strong CYP3A4 inhibitors is contraindicated
Contraindicated in patients with hepatic impairment
- Contraindicated for use with any degree of hepatic impairment
- Flibanserin exposure increased 4.5-fold in patients with hepatic impairment, compared with those with normal hepatic function, increasing the risk of hypotension, syncope, and CNS depression
Contraindications
Use with alcohoL
Coadministration with moderate or strong CYP3A4 inhibitors
Any degree of hepatic impairment
Cautions
Coadministration with alcohol increases the risk of severe hypotension and syncope (also see Contraindications and Black box warnings)
Coadministration with moderate or strong CYP3A4 inhibitors is significantly increases flibanserin concentrations, which can lead to hypotension and syncope (also see Contraindications, Black box warnings, and Dosing)
Concomitant use of multiple weak CYP3A4 inhibitors that may include herbal supplements (eg, ginkgo, resveratrol) or nonprescription drugs (eg, cimetidine) could also lead to clinically relevant increases in flibanserin concentrations that may increase the risk of hypotension and syncope
Causes CNS depression (eg, somnolence, sedation); risk of CNS depression is increased if taken during waking hours, or with alcohol or other CNS depressants, or with medications that increase flibanserin concentrations (eg, CYP3A4 inhibitors)
Hypotension and syncope can also occur with flibanserin taken alone
The use in patients with any degree of hepatic impairment is contraindicated; hepatic impairment significantly increases flibanserin concentrations, which can lead to hypotension and syncope
Pregnancy
Pregnancy
There are no studies in pregnant women to inform whether there is a drug-associated risk in humans
Animal data
- In animals, fetal toxicity only occurred in the presence of significant maternal toxicity, including reductions in weight gain and sedation
- Adverse reproductive and developmental effects consisted of decreased fetal weight, structural anomalies, and increases in fetal loss at exposures greater than 15 times exposures achieved with the recommended human dosage
Lactation
Unknown if distributed in human breast milk
Excreted in rat milk
Unknown whether flibanserin has effects on the breastfed infant or if it affects milk production
Because of the potential for serious adverse reactions, including sedation, in a breastfed infant, breastfeeding is not recommended during treatment
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Addyi (flibanserin)
Mechanism of action
Postsynaptic serotonin-1A (5HT-1A) receptor agonist and 5HT-2A receptor antagonist; also elicits moderate antagonist activities at the 5-HT2B, 5-HT2C, and dopamine D4 receptors
The mechanism of action HSDD is not known; may work by restoring prefrontal cortex control over the brain's motivation/rewards structures, enabling sexual desire to manifest; this may occur by increasing dopamine and norepinephrine while transiently decreasing serotonin in the brain's prefrontal cortex, which may be accomplished by reduced glutamate transmission
Absorption
Bioavailability: 33%
Peak plasma time: 0.75 hr
Peak plasma concentration: 419 ng/mL
AUC: 1543 ng·hr/mL
Food increased the extent of absorption and slowed the rate of absorption
Distribution
Protein bound: 98%, primarily to albumin
Metabolism
Primarily metabolized by CYP3A4 and, to a lesser extent, by CYP2C19
Elimination
Half-life: 11 hr
Excretion: 51% feces; 44% urine
Pharmacogenomics
CYP2C19 poor metabolizers had increased flibanserin exposures compared with CYP2C19 extensive metabolizers
Additionally, syncope occurred in a subject who was a CYP2C19 poor metabolizer
The frequencies of poor CYP2C19 metabolizers are ~2–5% among whites and blacks and ~2–15% among Asians
