First drug approved for treatment of sexual desire disorder

The U.S. Food and Drug Administration on August 18, 2015 approved Addyi (flibanserin) to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Prior to Addyi’s approval, there were no FDA-approved treatments for sexual desire disorders in men or women.

ADDYI is indicated for the treatment of 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 due to:

 A co-existing medical or psychiatric condition,

 Problems within the relationship, or
 The effects of a medication or other drug substance.

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

 ADDYI is not indicated for the treatment of HSDD in postmenopausal women or in men.

 ADDYI is not indicated to enhance sexual performance

DESCRIPTION

ADDYI (flibanserin) is a tablet for oral administration. The chemical name of flibanserin is 2HBenzimidazol-2-one, 1,3-dihydro-1-[2-[4-[3-(trifluoromethyl)phenyl]-1-piperazinyl]ethyl]. Its empirical formula is C20H21F3N4O and its molecular weight is 390.41. The structural formula is:

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CLINICAL PHARMACOLOGY

Mechanism of Action

The mechanism of action of ADDYI in the treatment of premenopausal women with hypoactive sexual desire disorder is not known.

 Pharmacodynamics

Receptor Binding:

In vitro, flibanserin demonstrated high affinity for the following serotonin (5-hydroxytryptamine or 5-HT) receptors: agonist activity at 5-HT1A and antagonist activity at 5-HT2A. Flibanserin also has moderate antagonist activities at the 5-HT2B, 5-HT2C, and dopamine D4 receptors.

———————-DOSAGE AND ADMINISTRATION———————–

 Recommended dosage is 100 mg taken once daily at bedtime

 ADDYI is dosed at bedtime because administration during waking hours increases risks of hypotension, syncope, accidental injury, and central nervous system (CNS) depression

 Discontinue treatment after 8 weeks if no improvement.

——————————-CONTRAINDICATIONS——————————

 Alcohol

 Moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors

 Hepatic impairment

———————–WARNINGS AND PRECAUTIONS————————

 Hypotension and Syncope with ADDYI Alone: Patients with pre-syncope should immediately lie supine and promptly seek medical help if symptoms do not resolve.

 Central Nervous System (CNS) Depression (e.g., Somnolence, Sedation): Can occur with ADDYI alone. Exacerbated by other CNS depressants, and in settings where flibanserin concentrations are increased. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how ADDYI affects them.

——————————ADVERSE REACTIONS——————————-

Most common adverse reactions (incidence ≥2%) are dizziness, somnolence, nausea, fatigue, insomnia, and dry mouth.

——————————DRUG INTERACTIONS——————————-

 Oral Contraceptives and Other Weak CYP3A4 Inhibitors: Increases flibanserin exposures and incidence of adverse reactions

 Strong CYP2C19 Inhibitors: Increases flibanserin exposure which may increase risk of hypotension, syncope, and CNS depression

 CYP3A4 Inducers: Use of ADDYI not recommended; flibanserin concentrations substantially reduced

 Digoxin: Increases digoxin concentrations, which may lead to digoxin toxicity. Increase monitoring of digoxin concentrations

 ———————–USE IN SPECIFIC POPULATIONS————————

 Nursing Mothers: ADDYI is not recommended.

 CYP2C19 Poor Metabolizers: Increases flibanserin exposure which may increase risk of hypotension, syncope, and CNS depression.