Expert Commentary
Flibanserin is poised for FDA approval. But why this drug? And why now?
Women with hypoactive sexual desire disorder have long sought a remedy for this common complaint. With an advisory committee recommending approval...
Although the drug was approved by the FDA, the agency was sufficiently concerned about some of its potential risks (see questions 4 and 5) that it implemented rigorous mitigation strategies (see question 7). Additional investigations were requested by the agency, including drug-drug interaction, alcohol challenge, and driving studies.
2. What are the indications?
Flibanserin is intended for use in premenopausal women who have acquired, generalized hypoactive sexual desire disorder (HSDD). That diagnosis no longer is included in the 5th edition of the Diagnostic and
Statistical Manual of Mental Disorders but is described in drug package labeling as “low sexual desire that causes marked distress or interpersonal difficulty and is not due to:
- a coexisting medical or psychiatric condition,
- problems within the relationship, or
- the effects of a medication or other drug substance.”1
- the effects of a medication or other drug substance.”
Although the drug has been tested in both premenopausal and postmenopausal women, it was approved for use only in premenopausal women. Also note inclusion of the term “acquired” before the diagnosis of HSDD, indicating that the drug is inappropriate for women who have never experienced a period of normal sexual desire.
3. How is HSDD diagnosed?
One of the best screening tools is the
Decreased Sexual Desire Screener, says
Dr. Krychman. It is available at http://obgynalliance.com/files/fsd/DSDS_Pocketcard.pdf. This tool is a validated instrument to help clinicians identify what HSDD is and is not.
4. Does the drug carry
any warnings?
Yes, it carries a black box warning about the risks of hypotension and syncope:
- when alcohol is consumed by users of the drug. (Alcohol use is contraindicated.)
- when the drug is taken in conjunction with moderate or strong CYP3A4 inhibitors or by patients with hepatic impairment. (The drug is contraindicated in both circumstances.) See question 9 for a list of drugs that are CYP3A4 inhibitors.
5. Are there any other risks worth noting?
The medication can increase the risks of hypotension and syncope even without concomitant use of alcohol. For example, in clinical trials, hypotension was reported in 0.2% of flibanserin-treated women versus less than 0.1% of placebo users. And syncope was reported in 0.4% of flibanserin users versus 0.2% of placebo-treated patients. Flibanserin is prescribed as a once-daily medication that is to be taken at bedtime; the risks of hypotension and syncope are increased if flibanserin is taken during waking hours.
The risk of adverse effects when flibanserin is taken with alcohol is highlighted by one case reported in package labeling: A 54-year-old postmenopausal woman died after taking flibanserin (100 mg daily at bedtime) for 14 days. This patient had a history of hypertension and hypercholesterolemia and consumed a baseline amount of 1 to 3 alcoholic beverages daily. She died of acute alcohol intoxication, with a blood alcohol concentration of 0.289 g/dL.1 Whether this patient’s death was related to flibanserin use is unknown.1
It is interesting to note that, in the studies of flibanserin leading up to the drug’s approval, alcohol use was not an exclusion, says Dr. Krychman. “Approximately 58% of women were self-described as mild to moderate drinkers. The clinical program was extremely large—more than 11,000 women were studied.”
Flibanserin is currently not approved for use in postmenopausal women, and concomitant alcohol consumption is contraindicated.
6. What is the dose?
The recommended dose is one tablet of
100 mg daily. The drug is to be taken at
bedtime to reduce the risks of hypotension, syncope, accidental injury, and central nervous system (CNS) depression, which can occur even in the absence of alcohol.
7. Are there any requirements for clinicians who want to prescribe the drug?
Yes. Because of the risks of hypotension, syncope, and CNS depression, the drug is subject to Risk Evaluation and Mitigation Strategies (REMS), as determined by the FDA. To prescribe the drug, providers must:
- review its prescribing information
- review the Provider and Pharmacy Training Program
- complete and submit the Knowledge Assessment Form
- enroll in REMS by completing and submitting the Prescriber Enrollment Form.
Before giving a patient her initial prescription, the provider must counsel her about the risks of hypotension and syncope and the interaction with alcohol using the Patient-Provider Agreement Form. The provider must then complete that form, provide a designated portion of it to the patient, and retain the remainder for the patient’s file.
For more information and to download the relevant forms, visit https://www.addyirems.com.
8. What are the most common
adverse reactions to the drug?
According to package labeling, the most common adverse reactions, with an incidence greater than 2%, are dizziness, somnolence, nausea, fatigue, insomnia, and dry mouth.
