Bremelanotide (Vyleesi) for Hypoactive Sexual Desire Disorder
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Bremelanotide (Vyleesi) for Hypoactive Sexual Desire Disorder
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Med Lett Drugs Ther. 2019 Jul 29;61(1577):114-6
 Select a term to see related articles  Addyi   bremelanotide   female sexual dysfunction   flibanserin   Vyleesi 
Bremelanotide (Vyleesi)
  • A melanocortin receptor agonist FDA-approved for treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder.
  • Increased sexual desire, but not the number of satisfying sexual events, and decreased distress associated with low sexual desire modestly more than placebo in two clinical trials.
  • Administered subcutaneously at least 45 minutes before anticipated sexual activity; maximum of 1 dose per 24 hours and 8 doses per month.
  • Can cause nausea, flushing, transient increases in blood pressure and decreases in heart rate, and focal hyperpigmentation of the face, gingiva, and breasts.
  • Contraindicated in patients with cardiovascular disease or uncontrolled hypertension.
  • No trials directly comparing bremelanotide with flibanserin (Addyi) are available to date.

The FDA has approved bremelanotide (Vyleesi – Amag), a melanocortin receptor agonist, for subcutaneous treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD). Bremelanotide is not approved for use in men or postmenopausal women. It is the second drug to be approved in the US for this indication; flibanserin (Addyi), which was approved in 2015, was the first.1

HSDD – HSDD is defined in the Vyleesi package insert as low sexual desire that causes marked distress or interpersonal difficulty and is not due to a coexisting medical or psychiatric condition, problems with a relationship, or the effects of medication. It has been characterized as lifelong or acquired and as generalized or situational (related to a specific partner, situation, or type of sexual activity).2 HSDD is no longer included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5); it has been replaced by Sexual Interest/Arousal Disorder (SIAD).

STANDARD TREATMENT – Initial management of HSDD has included psychotherapy and cognitive behavioral therapy.3,4 In clinical trials, flibanserin increased the frequency and intensity of sexual desire and the number of satisfying sexual events somewhat more than placebo in some women,1 but it has many drug interactions and it can cause hypotension, syncope, and CNS depression; alcohol consumption is contraindicated within 2 hours of taking the drug.5

MECHANISM OF ACTION – The mechanism of action of bremelanotide is unknown. The drug activates several melanocortin receptor subtypes including MC1R (expressed on melanocytes) and MC4R (expressed on neurons); MC4R is thought to play a role in female arousal, sexual desire, and orgasm.6

CLINICAL STUDIES – FDA approval of bremelanotide was based on the results of two unpublished, 24-week, double-blind trials (RECONNECT; summarized in the package insert) in 1247 premenopausal women with acquired, generalized HSDD of at least 6 months' duration. Women were randomized to self-administer bremelanotide or placebo approximately 45 minutes before anticipated sexual activity no more than once per 24 hours and 12 times per month.

In both trials, bremelanotide improved sexual desire and decreased distress associated with low sexual desire statistically significantly more than placebo (coprimary endpoints; see Table 2). About 25% of women treated with the drug had an increase of 1.2 or more in their sexual desire score compared to about 17% of those who took placebo and about 35% of women treated with bremelanotide had a decrease of 1 or more in their distress score compared to about 31% of those who took placebo. The number of satisfying sexual events was not significantly higher with bremelanotide than with placebo.7 Approximately 40% of women dropped out of the study before completion of the 24-week treatment period.

No trials directly comparing bremelanotide with flibanserin are available to date.

ADVERSE EFFECTS – In the RECONNECT trials, the most common adverse effects of bremelanotide were nausea (40%), flushing (20%), injection-site reactions (13%), headache (11%), and vomiting (5%). Antiemetic therapy was required in 13% of women taking the drug, and 8% discontinued treatment because of nausea. Discontinuation due to any adverse effect occurred in 18% of women taking bremelanotide and 2% of those taking placebo.

Transient increases in blood pressure and decreases in heart rate occur after each dose of bremelanotide and usually resolve within 12 hours; the drug is contraindicated for use in women with cardiovascular disease or uncontrolled hypertension.

Activation of MC1R by bremelanotide can lead to increased melanin expression; focal hyperpigmentation of the face, gingiva, and breasts occurred in 1% of patients who used up to 8 doses of the drug per month in the RECONNECT trials. The risk of hyperpigmentation was higher with more frequent dosing (it occurred in 38% of patients who used the drug daily for 8 days) and in patients with darker skin. The reversibility of hyperpigmentation after treatment discontinuation is not clear.

DRUG INTERACTIONS – Bremelanotide may slow gastric emptying and alter the rate and extent of absorption of oral drugs; it has been shown to decrease exposure to the opioid antagonist naltrexone. It may decrease the efficacy of drugs that depend on high peak concentrations for their desired effects, such as some antibiotics and analgesics. Unlike flibanserin, there are no restrictions on the use of alcohol with bremelanotide.

PREGNANCY AND LACTATION – There are no adequate studies on the use of bremelanotide in pregnant women. In animal studies, administration of bremelanotide caused fetal harm and adverse developmental effects in the offspring. Bremelanotide should not be used during pregnancy and women of childbearing age should use effective contraception during treatment.

There are no data on the presence of bremelanotide in human breast milk or on its effect on the breastfed infant or milk production.

DOSAGE, ADMINISTRATION, AND COST – The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 minutes before anticipated sexual activity. The duration of its efficacy is not known. No more than one dose of the drug should be used within 24 hours. Use of >8 doses of bremelanotide per month is not recommended; more frequent dosing increases the duration of its hypertensive effects and the risk of hyperpigmentation. The drug should be stopped after 8 weeks if symptoms of HSDD do not improve.

Bremelanotide is expected to become available through specialty pharmacies in September 2019. Its cost was not available at the time of publication.

CONCLUSION – In clinical trials, subcutaneous injection of the melanocortin receptor agonist bremelanotide (Vyleesi) 45 minutes before anticipated sexual activity was only modestly more effective than placebo in increasing sexual desire and decreasing distress associated with low sexual desire. It did not significantly increase the frequency of satisfying sexual events. Bremelanotide can cause nausea (often requiring antiemetic therapy), increases in blood pressure, decreases in heart rate, and focal hyperpigmentation.

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