Medical Editor: John P. Cunha, DO, FACOEP
Addyi (flibanserin) is a multifunctional serotonin agonist and antagonist (MSAA) indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and 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. Common side effects of Addyi include:
- insomnia, and
- dry mouth
Other side effects of Addyi include:
- abdominal pain,
- menstrual spotting,
- sedation, and
- spinning sensation (vertigo)
The recommended dosage of Addyi is 100 mg taken once daily at bedtime. Addyi may interact with alcohol, CNS depressants (such as diphenhydramine, opioids, hypnotics, benzodiazepines), antifungals, antiviral drugs, grapefruit juice, oral contraceptives, cimetidine, fluoxetine, ginkgo, ranitidine, proton pump inhibitors, selective serotonin reuptake inhibitors (SSRIs), some antibiotics, nefazodone, carbamazepine, phenobarbital, phenytoin, St. Johns Wort, digoxin, sirolimus, and some medicines used to treat high blood pressure, chest pain (angina), or other heart problems. Tell your doctor all medications and supplements you use. Addyi is only available through the Addyi risk evaluation and mitigation strategy (REMS) Program because of the increased risk of severe low blood pressure and fainting (loss of consciousness) with alcohol use. You can only get Addyi from pharmacies that are enrolled in the Addyi REMS Program. Tell your doctor if you are pregnant or plan to become pregnant before using Addyi. It is unknown if Addyi will harm a fetus. Because of the potential for serious adverse reactions including sedation in a breastfed infant, breastfeeding is not recommended during treatment with Addyi.
Our Addyi (flibanserin) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Hypotension and syncope [see WARNINGS AND PRECAUTIONS]
- CNS depression [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The approved 100 mg ADDYI dosage at bedtime was administered to 2,997 premenopausal women with acquired, generalized HSDD in clinical trials, of whom 1672 received treatment for at least 6 months, 850 received treatment for at least 12 months, and 88 received treatment for at least 18 months [see Clinical Studies].
Data from Five 24-Week, Randomized, Double-Blind Placebo-Controlled Trials in Premenopausal Women with HSDD
The data presented below are derived from five 24-week randomized, double-blind, placebo-controlled trials in premenopausal women with acquired, generalized HSDD. In these five trials, the frequency and quantity of alcohol use was not recorded. Three of these trials (Studies 1 through 3) also provided efficacy data [see Clinical Studies]. One of these trials (Study 5) did not evaluate the 100 mg bedtime dose.
In four trials, 100 mg ADDYI at bedtime was administered to 1543 premenopausal women with HSDD, of whom 1060 completed 24 weeks of treatment. The clinical trial population was generally healthy without significant comorbid medical conditions or concomitant medications. The age range was 18-56 years old with a mean age of 36 years old, and 88% were Caucasian and 9% were Black.
Serious adverse reactions were reported in 0.9% and 0.5% of ADDYI-treated patients and placebo-treated patients, respectively.
Adverse Reactions Leading to Discontinuation
The discontinuation rate due to adverse reactions was 13% among patients treated with 100 mg ADDYI at bedtime and 6% among patients treated with placebo. Table 1 displays the most common adverse reactions leading to discontinuation in four trials of premenopausal women with HSDD.
Table 1: Adverse Reactions* Leading to Discontinuation
in Randomized, Double-blind, Placebo-controlled Trials in Premenopausal Women
|*Adverse reactions leading to discontinuation of > 1% of patients receiving 100 mg ADDYI at bedtime and at a higher incidence than placebo-treated patients.|
Most Common Adverse Reactions
Table 2 summarizes the most common adverse reactions reported in four trials of premenopausal women with HSDD. This table shows adverse reactions reported in at least 2% of patients treated with ADDYI and at a higher incidence than with placebo [see WARNINGS AND PRECAUTIONS]. The majority of these adverse reactions began within the first 14 days of treatment.
Table 2: Common Adverse
Reactions* in Randomized, Double-blind, Placebo-controlled Trials in
Premenopausal Women with HSDD
|* Adverse reactions reported in ≥ 2% of patients receiving 100 mg ADDYI at bedtime and at a higher incidence than placebo-treated patients.|
Less Common Adverse Reactions
In four trials in premenopausal women with HSDD treated with 100 mg ADDYI at bedtime, less common adverse reactions (reported in ≥ 1% but < 2% of ADDYI-treated patients and at a higher incidence than with placebo) included:
- Anxiety (ADDYI 1.8%; placebo 1.0%),
- Constipation (ADDYI 1.6%; placebo 0.4%),
- Abdominal pain (ADDYI 1.5%; placebo 0.9%),
- Metrorrhagia (ADDYI 1.4%; placebo 1.4%),
- Rash (ADDYI 1.3%; placebo 0.8%),
- Sedation (ADDYI 1.3%; placebo 0.2%), and
- Vertigo (ADDYI 1%; placebo 0.3%).
In the five trials of premenopausal women with HSDD, appendicitis was reported in 6/3973 (0.2%) flibanserin-treated patients, while there were no reports of appendicitis in the 1905 placebo-treated patients.
In five trials of premenopausal women with HSDD, accidental injury was reported in 42/1543 (2.7%) ADDYI-treated patients and 47/1905 (2.5%) placebo-treated patients. Among these 89 patients who experienced injuries,9/42 (21%) ADDYI-treated patients and 3/47 (6%) placebo-treated patients reported adverse reactions consistent with CNS depression (e.g., somnolence, fatigue, or sedation) within the preceding 24 hours.
Adverse Reactions in Patients Who Reported Hormonal Contraceptive Use
In four trials of premenopausal women with HSDD, 1466 patients (43%) reported concomitant use of hormonal contraceptives (HC) at study enrollment. These trials were not prospectively designed to assess an interaction between ADDYI and HC. ADDYI-treated patients who reported HC use had a greater incidence of dizziness, somnolence, and fatigue compared to ADDYI-treated patients who did not report HC use (dizziness 9.9% in HC non-users, 13.4% in HC users; somnolence 10.6% in HC non-users, 12.3% in HC users; fatigue 7.5% in HC non-users, 11.4% in HC users). There were no meaningful differences in the incidence of these adverse reactions in placebo-treated patients who reported or did not report HC use [see DRUG INTERACTIONS].
Data from Other Trials
One death occurred in a 54 year-old postmenopausal woman treated with 100 mg ADDYI taken at bedtime (ADDYI is not approved for the treatment of postmenopausal women with HSDD) [see INDICATIONS AND USAGE]. This patient had a history of hypertension and hypercholesterolemia and baseline alcohol consumption of 1-3 drinks daily. She died of acute alcohol intoxication 14 days after starting ADDYI. Blood alcohol concentration on autopsy was 0.289 g/dL. The autopsy report also noted coronary artery disease. A relationship between this patient's death and use of ADDYI is unknown [see BOXED WARNING and WARNINGS AND PRECAUTIONS].
Hypotension, Syncope, and CNS Depression in Studies of Healthy Subjects
Hypotension, Syncope, and CNS Depression with Alcohol
In a cross-over alcohol interaction study of 100 mg ADDYI and alcohol in 25 healthy subjects dosed in the morning [see CLINICAL PHARMACOLOGY], somnolence was reported in 67%, 74%, and 92% of subjects who received ADDYI alone, ADDYI in combination with 0.4 g/kg ethanol, and ADDYI in combination with 0.8 g/kg ethanol, respectively. In the group receiving ADDYI in combination with 0.4 g/kg ethanol, 4/23 (17%) subjects had substantial reductions in blood pressure, resulting in hypotension and/or syncope requiring medical intervention. In the group receiving ADDYI in combination with 0.8 g/kg ethanol, 6/24 (25%) subjects experienced orthostatic hypotension [see BOXED WARNING, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS].
Hypotension and Syncope with Fluconazole
In a pharmacokinetic drug interaction study of 100 mg ADDYI and 200 mg fluconazole (a moderate CYP3A4 inhibitor, moderate CYP2C9 inhibitor, and a strong CYP2C19 inhibitor) in healthy subjects, hypotension or syncope requiring placement supine with legs elevated occurred in 3/15 (20%) subjects treated with concomitant ADDYI and fluconazole compared to no such adverse reactions in subjects treated with ADDYI alone or fluconazole alone. One of these 3 subjects became unresponsive with a blood pressure of 64/41 mm Hg and required transportation to the hospital emergency department where she required intravenous saline. Due to these adverse reactions, the study was stopped. In this study, the concomitant use of ADDYI and fluconazole increased flibanserin exposure 7-fold [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].
Syncope with Ketoconazole
In a pharmacokinetic drug interaction study of 50 mg flibanserin and 400 mg ketoconazole, a strong CYP3A4 inhibitor, syncope occurred in 1/24 (4%) healthy subjects treated with concomitant flibanserin and ketoconazole, 1/24 (4%) receiving flibanserin alone, and no subjects receiving ketoconazole alone. In this study, the concomitant use of flibanserin and ketoconazole increased flibanserin exposure 4.5-fold [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].
Syncope in Poor CYP2C19 Metabolizers
In a pharmacogenomic study of 100 mg ADDYI in subjects who were poor or extensive CYP2C19 metabolizers, syncope occurred in 1/9 (11%) subjects who were CYP2C19 poor metabolizers (this subject had a 3.2 fold higher flibanserin exposure compared to CYP2C19 extensive metabolizers) compared to no such adverse reactions in subjects who were CYP2C19 extensive metabolizers [see DRUG INTERACTIONS, Use In Specific Populations and CLINICAL PHARMACOLOGY].
Read the entire FDA prescribing information for Addyi (Flibanserin Tablets, for Oral Use)
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