General

**REMS Drug**

Genetic Implications:

Pronunciation:
flib- an-ser-in

Trade Name(s)

• Addyi

Ther. Class.
sexual dysfunction agents

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–HT_1A  receptors and antagonist activity at 5–HT_2A  receptors; also has moderate antagonist activity at 5–HT_2B , 5–HT_2C , and dopamine D₄  receptors.

Therapeutic Effect(s):

↑ sexual desire with ↓ distress 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 significantly ↑ flibanserin concentrations and an ↑ risk 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)

Contraindication/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 (↑ risk 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

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

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  verapamil  ↑ blood 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  alcohol  ↑ 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 also ↑ blood 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  antifungals  ↑ blood 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  rifapentine  ↓ blood levels and effectiveness; concurrent use in not recommended.
• ↑  digoxin  and  sirolimus  levels and risk of toxicity; careful monitoring recommended
• ↑ risk of CNS depression with other  CNS depressants  including alcohol, antihistamines, opioids, sedative/hypnotics, some anti-anxiety agents, antidepressants, and  antipsychotics .

Natural-Natural:

• Concurrent use with  ginko  may also ↑ blood levels, effects and the risk of adverse reactions; avoid use with other weak CYP3A4 inhibitors.
•  St. John's wort  ↓ blood levels and effectiveness; concurrent use is not recommended.

Drug-Food:

Concurrent ingestion of grapefruit juice ↑ blood 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

Assessment

• Assess sexual desire and related distress and interpersonal dysfunction before and periodically during therapy.
• Monitor for hypotension and syncope. Have patient lie supine if dizziness occurs.
• Assess likelihood of 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; interaction with alcohol increases risk of hypotension and syncope.

Potential Diagnoses

• Sexual dysfunction (Indications) 
• Risk for injury (Adverse Reaction) 

Implementation

• Administer once daily at bedtime; administration during waking hrs increases risks of hypotension, syncope, accidental injury, and central nervous system (CNS) depression.
• Only available through a restricted program,  Addyi REMS Program  due to increased risk of severe hypotension and syncope interaction with alcohol.

Patient/Family Teaching

• Instruct patient to take flibanserin as directed. If dose is missed, omit and take next dose at bedtime on next day. Advise patient to read  Patient Information  before starting therapy and with each Rx refill in case of changes.
• Advise patient to avoid grapefruit juice during therapy.
• Caution patient to avoid alcohol during therapy; increases hypotensive effects. May cause dizziness and fainting.
• Advise patient if dizziness occurs, immediately lie supine and promptly seek medical help if symptoms do not resolve.
• May cause drowsiness. Caution patient to avoid driving and other activities requiring alertness until 6 hrs after each dose or until response to medication is known.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
• Advise patient to notify health care professional if pregnancy is planned or suspected and to avoid breast feeding.

Evaluation/Desired Outcomes

Increase in sexual desire. If no improvement in 8 wk, discontinue flibanserin.