flibanserin (flib- an-ser-in) Addyi

 Indications

Treatment of premenopausal women with hypoactive

sexual desire disorder (HSDD) unrelated to concurrent

medical/psychiatric diagnoses, relationship issues, or

substance abuse. Does not enhance sexual performance.

Action

May be explained by agonist activity at 5–HT1A receptors

and antagonist activity at 5–HT2A receptors; also has moderate antagonist activity at 5–HT2B, 5–HT2C,

and dopamine D4 receptors. Therapeutic Effects:

qsexual desire withpdistress and interpersonal dysfunction.

Pharmacokinetics

Absorption: Moderately absorbed (33%) following

oral administration.

Distribution: Unknown.

Protein Binding: 98%.

Metabolism and Excretion: Highly metabolized,

mostly by the CYP3A4 enzyme system with lesser

metabolized by CYP2C19; the CYP2C19 enzyme system

exhibits genetic polymorphism; poor metabolizers may

have significantlyqflibanserin concentrations and an

qrisk of adverse effects. 44% excreted in urine, 51% in

feces almost entirely as metabolites which do not appear

to be pharmacologically active.

Half-life: 11 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO within 1 hr 1 hr 24 hr

Contraindications/Precautions

Contraindicated in: Alcohol ingestion (excess risk

of hypotension/syncope); Concurrent use of strong/

moderate CYP3A4 inhibitors; Concurrent use of

CYP3A4 inducers; Hepatic impairment; Lactation:

Breast feeding is not recommended.

Use Cautiously in: CYP2C19 poor metabolizers

(qrisk of adverse reactions including hypotension, syncope,

and drowsiness); Geri: Not indicated for use in

the elderly; OB: Safe use during pregnancy has not been

established; Pedi: Not indicated for use in children.

Adverse Reactions/Side Effects

CNS: dizziness, drowsiness, anxiety, fatigue, insomnia,

vertigo. CV: HYPOTENSION/SYNCOPE. GI: nausea, constipation,

dry mouth. Derm: rash.

Interactions

Drug-Drug: Concurrent use of strong or moderate

CYP3A4 inhibitors including atazanavir, ciprofloxacin,

clarithromycin, conivaptan, diltiazem,

erythromycin, fluconazole, fosamprenavir, indinavir,

itraconazole, ketoconazole, indinavir, nelfinavir,

posaconazole, ritonavir, saquinavir, and

verapamilqblood levels, effects and risk of serious

adverse reactions; concurrent use is contraindicated.

Wait two wk after discontinuing inhibitor before initiating

fibanserin. If initiating inhibitor, wait two days after

last dose of flibanserin. Concurrent use with alcoholq

risk of hypotension/syncope and excess sedation; concurrent

use is contraindicated. Concurrent use of oral

hormonal contraceptives and weak CYP3A4 inhibitors

including cimetidine, fluoxetine, and ranitidine

may alsoqblood levels, effects and the risk of

adverse reactions; avoid use of multiple weak CYP3A4

inhibitors. Strong CYP2C19 inhibitors including

proton pump inhibitors, SSRIs, benzodiazepines,

and antifungalsqblood levels, effects, and the risk of

adverse reactions including hypotension, syncope, and

CNS depression; concurrent use should be undertaken

with caution. CYP3A4 inducers including carbamazepine,

phenobarbital, phenytoin, rifabutin, rifampin,

and rifapentinepblood levels and effectiveness;

concurrent use in not recommended.qdigoxin

and sirolimus levels and risk of toxicity; careful monitoring

recommended.qrisk of CNS depression with

other CNS depressants including alcohol, antihistamines,

opioids, sedative/hypnotics, some antianxiety

agents, antidepressants, and antipsychotics.

Natural-Natural: Concurrent use with ginko may

alsoqblood levels, effects and the risk of adverse reactions;

avoid use with other weak CYP3A4 inhibitors. St.

John’s wortpblood levels and effectiveness; concurrent

use is not recommended.

Drug-Food: Concurrent ingestion of grapefruit

juiceqblood levels, effects, and risk of hypotension/

syncope; concurrent ingestion is contraindicated.

Route/Dosage

PO (Adults): 100 mg once daily (at bedtime).

Availability

Tablets: 100 mg.