Here are some important drug facts to review before Addyi launches in October.
The FDA recently approved flibanserin (Addyi), the first drug to treat hypoactive sexual desire disorder (HSDD) in women.
Prior its approval, the drug was heavily endorsed by women’s groups and coalitions that noted several drugs for sexual activity existed for men (e.g. sildenafil), but there were no such medications on the market for women.
Because it has been suggested that Addyi’s approval was needed to “even the score,” it has sometimes been referred to as the “pink” or “female Viagra,” even though it has no relationship to the mechanism or indication of that drug.
While Valeant scrambles to assemble its sales force and marketing strategy for the drug’s official launch next month, pharmacists need to prepare themselves to answer some basic questions about Addyi.
Here are some important drug facts to review:
Although a drug’s regulatory history doesn’t usually play a role in the pharmacist’s clinical perspective, it is a good idea to at least be armed with the fact that flibanserin was twice rejected by the FDA in 2010 and 2013 for unimpressive results and concerning side effects and drug interactions.
This doesn’t take away from the fact that Addyi was eventually approved, but it may at least make pharmacists aware that its pathway to the market was far from easy. The advisory committee that recommended the recent FDA approval did so by a majority vote of 18 to 6.
Flibanserin is indicated to treat hypoactive sexual desire disorder, also known as low libido. This condition is not primarily about lack of “arousal” (like sildenafil) or even about orgasm; rather, it is related to interest or desire for sexual intimacy.
Additionally, flibanserin is only indicated to treat “acquired” and “generalized” HSDD in premenopausal women. This means that libido has decreased from previous levels and different circumstances or partners did not change the patient’s lack of interest in sex.
Finally, an HSDD diagnosis requires that other factors that may cause low libido have been ruled out (e.g. medications, relationship issues, or medical problems) and that the condition causes marked personal distress.
While other prescription medications targeting hormonal imbalances (e.g. testosterone or estrogen) have been prescribed off-label for low libido in women, Addyi is the first drug approved specifically for HSDD, and it is not a hormonal therapy.
Addyi is available in a pink 100 mg tablet that is taken once a day, always at bedtime.
This bedtime dosing is very important because the medication may cause significant hypotension, syncope, CNS depression, and possibly injury if taken during waking hours. In addition, patients should not drive for at least 6 hours after taking the dose.
4. Mechanism of action
How does flibanserin work? A full answer that considers the concepts of macrocircuits in the brain, reward processing, and neurotransmitter function is beyond the scope of this review.
Put briefly, flibanserin is described as a multifunctional serotonin agonist and antagonist that enhances the release of dopamine and norepinephrine while decreasing serotonin release. Most patients will be satisfied to understand that this is not a hormonal approach, but a neurotransmitter approach designed to improve the “desire” center of the brain.
5. Alcohol use
Use of alcohol is a contraindication for Addyi treatment. The concern is so serious that the FDA demands a specific REMS program for the drug that requires both prescribers and pharmacists to be educated on this important counseling point.
6. Drug interactions
Flibanserin is also contraindicated when combined with moderate to strong CYP3A4 inhibitors. For example, fluconazole should not be used while a woman is taking flibanserin.
Other commonly prescribed or ingested examples of moderate or strong CYP3A4 inhibitors include ketoconazole, itraconazole, clarithromycin, telaprevir, ciprofloxacin, and grapefruit juice.
Patients should also be warned about the risk of concomitant flibanserin use with other common CNS depressants such as diphenhydramine, opioids, and benzodiazepines.
7. Clinical trial results
Does Addyi work? Given the price Valeant paid for the drug, this is the billion-dollar question.
Suffice it to say that women taking flibanserin in 3 efficacy trials over 24 weeks had significant improvement in several measurable areas related to improved sex drive. For example, study participants had an average of about 2 additional “satisfying sexual events” (SSE) compared to an increase of just 1 SSE in the placebo group. These are far from miraculous results, but they are an improvement nonetheless.
Will Addyi be a hero or a zero when it comes to marketing, sales, and success? The drug is being marketed as “the first of her kind,” but will it also be the last?
At this point, it is still hard to say. But given the drug’s large market potential and the fact that it stands alone as an approved treatment in this category, there is a chance that it might do very well. If so, it would be a satisfying financial event for Valeant.