Avoid the ‘Pink Pill’ Flibanserin (ADDYI) for Low Female Sexual Desire

In August 2015, the Food and Drug Administration (FDA) approved the oral drug flibanserin (ADDYI) to treat acquired hypoactive sexual desire disorder — characterized by generalized low sexual desire (that is not due to an adverse drug effect or substance use, health condition or relationship problems) that causes marked distress — for use in women who have not reached menopause.[1] This approval was contrary to the recommendations of the FDA’s own experts and also negated the agency’s earlier position when it rejected the drug in 2010 and 2013.[2]

In June 2015, Public Citizen’s Health Research Group testified before two FDA advisory committees, urging the agency to again reject flibanserin because the drug’s life-threatening risks far exceed its very minimal benefit.[3] Therefore, we have classified flibanserin as Do Not Use.

After failing to gain market share (due to bungled promotional efforts and a subsequent shareholder lawsuit against Valeant, the drug’s owner at the time),[4] flibanserin has been relaunched by its original owner, Sprout Pharmaceuticals, with a shrewd marketing campaign.[5] This campaign utilizes the color pink, trying to make women think that they have “stumbled onto the key to the puzzle of female desire… [that] can be unlocked with a prescription.”[6] Additionally, the campaign offers a free eight-week trial of flibanserin that women can easily obtain by clicking on a link on the drug’s promotional website. The link directs them to a telemedicine provider that will prescribe the drug for a small consultation fee.

Marginal benefit

Flibanserin is often erroneously dubbed the “female VIAGRA” (generic name sildenafil). However, sildenafil affects sexual performance in men with erectile dysfunction by increasing blood flow to the penis. In contrast, flibanserin does not enhance sexual performance, and the manner in which it allegedly stimulates sexual desire is unknown.[7] Whereas sildenafil can be taken on an as-needed basis shortly before sexual activity, flibanserin must be taken every night at bedtime and takes a few weeks of use to show any beneficial effect.

In fact, the benefit of flibanserin in clinical trials was described as “numerically small” by FDA experts.[8] Specifically, the drug resulted in a median increase of only one-half to one additional satisfying sexual experience per month compared with placebo in clinical trials (women had a median of about two to three satisfying sexual experiences at the beginning of the trial).

Similarly, compared with placebo, flibanserin resulted in only minimal improvements on survey questions that measured either sexual desire or feelings of distress in small clinical trials. FDA experts also had concerns about the validity of the survey questions used to assess sexual desire in these trials.

Furthermore, a well-conducted 2016 systematic review of data from eight randomized clinical trials (three of which were not published) that together enrolled nearly 6,000 women showed that the benefits of flibanserin were “marginal,” particularly when its adverse effects were taken into account.[9]

Dangerous adverse effects

In addition to its minimal benefits, flibanserin causes serious adverse effects. Of greatest concern, the drug can cause severe hypotension (low blood pressure) and syncope (passing out) — especially in patients who use alcohol or have liver problems — possibly leading to serious or life-threatening accidents or injuries.[10]

The interaction of flibanserin with alcohol prompted the FDA to mandate that, as a condition of approval, the drug’s product labeling carry a black-box warning — the strongest warning required by the FDA — indicating that women must abstain from alcohol use completely if they take the drug.[11] The agency also required the drugmaker to conduct postmarketing studies on the interaction of the drug with alcohol.

Based on the results of the postmarketing studies, the FDA compelled the drugmaker in 2019 to retain the black-box warning but recklessly “diluted” this warning by removing the absolute directive that women taking the drug completely abstain from alcohol use.[12] Specifically, the revised warning now only indicates that flibanserin should not be taken for at least two hours after consuming one or more standard alcoholic drinks (such as one 12-ounce regular beer) in the evening. Notably, in allowing this labeling change, the FDA failed to adequately consider the fact that there were significant missing or delayed blood pressure measurements when flibanserin and alcohol were used together compared with when alcohol or flibanserin was used alone in the postmarking studies, which undermined the validity of the study results.

Flibanserin also can cause central nervous system depression, which can lead to drowsiness, sedation and fatigue. In five clinical trials, such adverse effects occurred in 21% of women taking flibanserin at bedtime and only 8% of women taking a placebo. Because of these adverse effects, the product labeling for flibanserin indicates that the drug should be taken at bedtime.

Other less serious but quite common adverse effects of flibanserin include dry mouth, insomnia and nausea.

Importantly, taking flibanserin concurrently with numerous medications that interfere with the body’s breakdown of the drug, including digoxin (LANOXIN) and oral contraceptives, further increases the risks of hypotension and syncope.

Questionable FDA approval

After the FDA rejected flibanserin in 2013, Sprout Pharmaceuticals launched an aggressive lobbying and marketing campaign that involved the creation of a sham advocacy group called “Even the Score” and accusations of gender bias by the agency.[13] The centerpiece of this campaign were claims that the FDA had approved several medications for sexual dysfunction for men but none for women. These claims are baseless because, among other things, the agency has not approved any low sexual desire medications for men.

Experts took issue with the FDA approval of flibanserin. For example, Dr. Adriane Fugh-Berman of Georgetown University commented that “marketing won over science” in this case.[14] Researchers from the Dartmouth-Hitchcock Medical Center argued that flibanserin’s approval for “a non–life-threatening condition” was not warranted given the “substantial — and unnecessary — uncertainty about its dangers.”[15] Others warned that although the FDA has approved flibanserin for a narrow group of women, it will undoubtedly be used off-label by a wider population of women who may not meet the criteria for hypoactive sexual desire disorder, or who may have conditions or be taking other medications that increase their risk of experiencing the drug’s adverse effects.[16]

What You Can Do

If you are a woman who is burdened by persistent low sexual desire, do not take flibanserin. Also, do not use the more recently approved bremelanotide (VYLEESI)[17] because — contrary to the claims of lucrative pharmaceutical companies — there is no miracle drug to boost female libido. Instead, take an integrative approach to address the underlying factors (whether they are cultural, psychological or relational) that may be impacting your condition.
 

References

[1] Sprout Pharmaceuticals. Label: flibanserin (ADDYI). October 2019: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022526s009lbl.pdf. Accessed February 6, 2020.

[2] Food and Drug Administration. Summary review for new drug application number 022526Orig1s000. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000SumRedt.pdf. Accessed February 6, 2020.

[3] Public Citizen. Testimony before the joint meeting of the Bone, Reproductive, and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee regarding flibanserin. June 4, 2015. https://www.citizen.org/article/testimony-before-the-fdas-bone-reproductive-and-urologic-drugs-advisory-committee-and-the-drug-safety-and-risk-management-advisory-committee-regarding-flibanserin/#overlay-context=. Accessed February 6, 2020.

[4] Sorscher S. Maker of ‘female Viagra’ sued as sales fizzle. Health Letter. June 2017. https://www.citizen.org/news/maker-of-female-viagra-sued-as-sales-fizzle/. Accessed February 6, 2020.

[5] Sprout Pharmaceuticals.addyi (flibanserin). https://addyi.com/. Accessed February 6, 2020.

[6] Luscombe B. This CEO is pushing a pill for female sex drive. But does the science hold up? Time. November 8, 2018. https://time.com/5448807/female-desire-pill/. Accessed February 6, 2020.

[7] Sprout Pharmaceuticals. Label: flibanserin (ADDYI). October 2019: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022526s009lbl.pdf. Accessed February 6, 2020.

[8] Food and Drug Administration. Summary review for new drug application number 022526Orig1s000. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/022526Orig1s000SumRedt.pdf. Accessed February 6, 2020.

[9] Jaspers L, Feys F, Bramer WM, et al. Efficacy and safety of flibanserin for the treatment of hypoactive sexual desire disorder in women: A systematic review and meta-analysis. JAMA Intern Med. 2016;176(4):453-462.

[10] Sprout Pharmaceuticals. Label: flibanserin (ADDYI). October 2019: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022526s009lbl.pdf. Accessed February 6, 2020.

[11] Sprout Pharmaceuticals. Label: flibanserin (ADDYI). August 2015: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022526lbl.pdf. Accessed February 5, 2020.

[12] Food and Drug Administration. FDA news release: FDA orders important safety labeling changes for Addyi. April 11, 2019. https://www.fda.gov/news-events/press-announcements/fda-orders-important-safety-labeling-changes-addyi. Accessed February 6, 2020.

[13] Hogenmiller A, Hirsch A, Fugh-Berman A. The score is even. The Hasting Center Bioethics Forum. June 14, 2017. https://www.thehastingscenter.org/the-score-is-even/. Accessed February 6, 2020.

[14] Roehr B. FDA committee recommends approval for “female Viagra.” BMJ. 2015;350(June 5):h3097.

[15] Woloshin S, Schwartz LM. US food and drug administration approval of flibanserin: Even the score does not add up. JAMA Intern Med. 2016;176(4):439-442.

[16] Gellad WF, Flynn KE, Alexander GC. Evaluation of flibanserin science and advocacy at the FDA. JAMA. 2015;314(9):869-870.

[17] AMAG Pharmaceuticals. Label: bremelanotide (VYLEESI). June 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/210557s000lbl.pdf. Accessed January 22, 2020.