Flibanserin

Multimodal serotonergic; HSDD treatment

Flibanserin

Addyi

Flibanserin is the first FDA-approved medicine for premenopausal generalized acquired hypoactive sexual desire disorder (HSDD), 2015. Dosed at bedtime nightly because of significant CNS depression; effects emerge gradually over weeks. Carries a BLACK BOX warning about hypotension and syncope with alcohol or moderate-to-strong CYP3A4 inhibitors.

Experience

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Problems

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Titration strategies

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Effects

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Pharmacokinetics

Absorption

Peak in ~45 min.

Distribution

Plasma protein binding ~98%.

Metabolism

Hepatic; CYP3A4 primary, CYP2C19 minor.

Elimination

Fecal and renal as metabolites.

Interactions

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Monitoring

Blood pressure; sedation; alcohol use.

Patient counseling

Avoid alcohol — combination causes severe hypotension and syncope. Avoid strong/moderate CYP3A4 inhibitors. Take at bedtime to minimize sedation. Effects on desire emerge over 8 weeks; discontinue if no benefit by then.

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See also

Bupropion (off-label for SSRI-induced sexual side effects)

References

Pharmacy

Starting dose

100 mg at bedtime daily

Preparations

100 mg tabs

US FDA Max

100 mg/d

Common uses

Classification(s)

Classes

Multimodal serotonergic; HSDD treatment

Pharmacology

Routes

Oral

Onset

Effects accumulate over weeks; assess at 8 weeks

Duration

Continuous daily dosing

Half-life

~11 h

Bioavailability

~33%

Pregnancy

Not indicated; pregnancy effects unknown

Legal status

Rx-only in US (REMS program)

Purported mechanism

5-HT1A agonist, 5-HT2A antagonist, with weaker activity at D4 and other receptors. Net effect involves enhanced prefrontal dopaminergic/noradrenergic tone with decreased serotonergic inhibition of sexual desire.