Executive Summary
The Food and Drug Administration has approved Addyi (flibanserin, Sprout Pharmaceuticals) to treat acquired, generalized hypoactive sexual desire disorder in premenopausal women. The drug is the first such treatment to be approved for this condition.
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Hypoactive sexual desire disorder, or HSDD, is characterized by low sexual desire that causes marked distress or interpersonal difficulty. The condition 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.
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Addyi’s boxed warning highlights the risks of severe hypotension and syncope in patients who drink alcohol during treatment with the drug, in those who also use moderate or strong cyp3a4 inhibitors, and in those who have liver impairment. The drug is contraindicated in these patients.
The Food and Drug Administration (FDA) has approved Addyi (flibanserin, Sprout Pharmaceuticals, Raleigh, NC) to treat acquired, generalized hypoactive sexual desire disorder in premenopausal women. The drug is the first such treatment to be approved by the FDA for this condition.
At press time, Laval, Quebec-based Valeant Pharmaceuticals International and Sprout Pharmaceuticals had entered into a definitive agreement under which a wholly owned subsidiary of Valeant will acquire Sprout, with Addyi to be available in the fourth quarter of 2015.
Hypoactive sexual desire disorder, or HSDD, is characterized by low sexual desire that causes marked distress or interpersonal difficulty. The condition 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. Research indicates the condition is thought to affect one in 10 women.1
Originally developed as an antidepressant, flibanserin works on three neurotransmitters: dopamine, norepinephrine, and serotonin. Flibanserin works by increasing levels of dopamine and norepinephrine, while dropping levels of serotonin. This drug interaction is intended to increase chemicals that help promote sexual desire and decrease the one that can suppress desire.
The path to what some have dubbed “the female Viagra” has been a rocky one. The drug initially was researched by German drug company Boehringer Ingelheim for hypoactive sexual desire disorder. An FDA advisory committee rejected it in 2010. Sprout Pharmaceuticals acquired rights to the drug in 2011, and it resubmitted an FDA new drug application in 2013. The regulatory agency rejected Sprout Pharmaceuticals’ initial submission, and it requested additional studies for drug-drug interactions and a driving study to test the effects of sleepiness.
In October 2014, the FDA held a public hearing on female sexual dysfunction in response to a call from the Washington, DC-based advocacy organization Even the Score, a coalition of 26 national women’s rights and women’s health organizations, including the Association of Reproductive Health Professionals, the National Association of Nurse Practitioners in Women’s Health, the American College of Nurse-Midwives, and the American Sexual Health Association. Sprout Pharmaceuticals resubmitted the drug in February 2015 with the additional requested data. An FDA advisory committee voted 18-6 in June 2015 to recommend approval of the drug.
Women negatively impacted by hypoactive sexual desire disorder deserve a wide range of beneficial treatment options, which, in addition to healthy diets, appropriate exercise, and psychotherapy and counseling, now includes a specific drug therapy option, says Wayne Shields, president and chief executive officer of the Association of Reproductive Health Professionals.
Prior to the approval of flibanserin, women had no approved medical treatment options for their condition, while 26 options are available for male sexual dysfunctions, said Susan Scanlan, chair of Even the Score, in a released statement.
It comes down to choice for women and their providers, says Lynn Barclay, chief executive officer of the American Sexual Health Association. There is seldom a “one-size-fits-all” answer to the many challenges people face in achieving and maintaining sexual health and satisfying sex lives, she states.
“We believe both men and women, as well as their healthcare providers, should have choices in addressing sexual dysfunction,” states Barclay. “We also believe that women and men can be trusted to decide for themselves about using an FDA-approved and healthcare provider-prescribed treatment option.”
Boxed warning
Addyi comes with a boxed warning to highlight the risks of severe hypotension and syncope in patients who drink alcohol during treatment with the drug, in those who also use moderate or strong CYP3A4 inhibitors, and in those who have liver impairment. The drug is contraindicated in these patients. In addition, the FDA is requiring that three studies in women be conducted to better understand the known serious risks of the interaction between Addyi and alcohol.
Patients using flibanserin should take the drug, dosed as a 100-mg tablet, at bedtime to help decrease the risk of adverse events occurring due to possible hypotension, syncope, and central nervous system depression, such as sleepiness and sedation. Women should discontinue treatment after eight weeks if they do not report an improvement in sexual desire and associated distress. The most common adverse reactions associated with drug use are dizziness, somnolence, nausea, fatigue, insomnia, and dry mouth.
The approval comes with the following risk evaluation and mitigation strategy:
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Clinicians must be trained and certified to prescribe Addyi. Further information, including a list of pharmacies qualified to dispense Addyi, is available at AddyiREMS.com (See “Search for a Certified Pharmacy near you”) or call (844) 746-5745.
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Providers must counsel patients and make sure they are aware of the increased risk for hypotension and syncope associated with use of the drug. Patients also must be warned about the risks of using alcohol while taking Addyi.
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Dispensing pharmacies must undergo a training and certification process to dispense the drug.
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Pharmacies may fill only those prescriptions written by certified providers.
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Before dispensing Addyi, pharmacists must counsel patients not to drink alcohol while taking the drug.
Sprout Pharmaceuticals is focused on the education of prescribers and pharmacies, including education around the validated screening tool called the Decreased Sexual Desire Screener, says company spokesperson Julia Cohen. (See screener questions at http://bit.ly/1PZqKt6.)
“This tool takes the practitioner and patient through five specific questions, and excludes a diagnosis of HSDD if the patient is taking certain medications or has certain comorbidities that could possibly explain their distressing low desire,” says Cohen. “If there are any other contributing factors present, this would result in the conclusion that the patient does not have HSDD and is not a candidate for Addyi.”
Who will benefit?
Not all women will receive relief from HSDD with flibanserin. In one trial, the proportion of participants who indicated they had experienced a meaningful benefit from study medications was 44.7% with flibanserin and 34.8% with placebo.2 In another trial, these percentages were 38.6 and 26.7, respectively.3
Andrew Kaunitz, MD, University of Florida Research Foundation professor and associate chairman of the Department of Obstetrics and Gynecology at the University of Florida College of Medicine — Jacksonville, observes that hypoactive sexual desire disorder is difficult to treat and represents a “frustrating condition” for women, their partners, and clinicians. Clinicians caring for women will be fielding numerous questions regarding this new medication, notes Kaunitz.
“One challenge we will face will be to help premenopausal women with HSDD to understand that, in most cases, flibanserin will, at most, generate a ripple, rather than a torrent of increased desire,” states Kaunitz. “Attention to concomitant alcohol and medication use will be important to minimize adverse outcomes with use.” [Contraceptive Technology Update posted a story on Aug. 19, 2015, at reliasmedia.com about the approval. If you didn’t receive an email notice about the story, then we don’t have your email address. To receive breaking news, contact customer service at (800) 688-2421 or [email protected] to give us your email address.]
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Shifren JL, Monz BU, Russo PA, et al. Sexual problems and distress in United States women: Prevalence and correlates. Obstet Gynecol 2008; 112(5):970-978.
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Katz M, DeRogatis LR, Ackerman R, et al; BEGONIA trial investigators. Efficacy of flibanserin in women with hypoactive sexual desire disorder: Results from the BEGONIA trial. J Sex Med 2013; 10(7):1807-1815.
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Derogatis LR, Komer L, Katz M, et al; VIOLET Trial Investigators. Treatment of hypoactive sexual desire disorder in premenopausal women: Efficacy of flibanserin in the VIOLET Study. J Sex Med 2012; 9(4):1074-1085.
