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Flibanserin (Addyi) - Uses, Dose, Side effects, MOA, Brands

Flibanserin is a medication primarily used to treat hypoactive sexual desire disorder (HSDD) in premenopausal women. HSDD is characterized by a persistent lack of sexual desire that causes distress or interpersonal difficulty. Flibanserin works by affecting serotonin and dopamine levels in the brain. Unlike other medications for sexual dysfunction, which primarily affect blood flow, flibanserin targets neurotransmitters in the brain.

Originally developed as an antidepressant, flibanserin was later found to have potential benefits in treating HSDD. It is taken daily and needs to be taken for several weeks to start showing effectiveness. Common side effects may include dizziness, drowsiness, nausea, fatigue, and dry mouth.

Flibanserin (Addyi) is used in the treatment with premenopausal women with a reduced libido or women who have a hypoactive sexual disorder. Hypoactive sexual disorder is considered as the most common form of female sexual disorders.

Flibanserin (Addyi) Uses:

Hypoactive sexual desire disorder:
- It is indicated for the treatment of hypoactive sexual disorder in premenopausal women characterized by a reduced sexual desire that causes marked interpersonal difficulty and distress. Hypoactive disorder is not secondary to a psychiatric or coexisting medical disorder, secondary to the effects of medications, drugs or substance use, or relationship problems.
- Limitations of use:
  - It is not indicated for the treatment of hypoactive sexual disorder in men or postmenopausal women, or to enhace sexual performance.

Flibanserin (Addyi) Dose in Adults

Flibanserin (Addyi) Dose in the treatment of Hypoactive sexual desire disorder:

Flibanserin is a medication used to treat low sexual desire in women who haven't gone through menopause.
The usual dose is 100 milligrams once a day before bedtime.
Doctors typically check if the treatment is working after about 8 weeks.
If it's not helping, they might stop the treatment.

Missed dose:

If you forget to take a dose, just skip it and take the next dose at bedtime as usual.

Dosage adjustment for the transition to or from treatment with a moderate or strong CYP3A4 inhibitors:

f you're starting a medication that affects flibanserin, wait at least 2 days after your last dose of flibanserin before starting the new medication.
If you're starting flibanserin after taking a medication that affects it, wait at least 2 weeks after your last dose of the other medication before starting flibanserin.

Dose in children:

Not indicated.

Flibanserin (Addyi) Pregnancy risk category: N

In certain animal studies, adverse events were noted during reproduction.
This suggests that there may be potential risks associated with using the medication during pregnancy or while trying to conceive.

Flibanserin use during breastfeeding:

The presence of flibanserin in breast milk and its potential effects on nursing infants are not fully understood.
Because of the possibility of adverse reactions in infants, such as sedation, the manufacturer does not recommend breastfeeding while taking flibanserin.

Flibanserin (Addyi) Dose in Kidney Disease:

The manufacturer's labeling for flibanserin does not specify any dosage adjustments based on renal impairment.
This suggests that individuals with mild to severe kidney problems may not need to adjust their dosage because the medication's effects on the body are not significantly altered in these patients.

Dose in Liver disease:

Use is contraindicated.

Common Side Effects of Flibanserin (Addyi):

Central nervous system:
- Dizziness
- Drowsiness

Less Common Side Effects of Flibanserin (Addyi):

Central nervous system:
- Fatigue
- Insomnia
- Anxiety
- Sedation
- Vertigo
Gastrointestinal:
- Nausea
- Abdominal pain
- Constipation
- Xerostomia

Contraindication to Flibanserin (Addyi):

In Canadian labeling, there are additional contraindications compared to US labeling for the use of flibanserin. These include:

Hypersensitivity: Individuals who are hypersensitive to flibanserin or any of its components should not use the medication.
Low Blood Pressure with Alcohol: Flibanserin should not be used in patients with a resting systolic blood pressure less than 110 mm Hg or diastolic blood pressure less than 60 mm Hg when combined with alcohol.
Pregnancy: Flibanserin is contraindicated during pregnancy due to potential risks to the fetus.
Breastfeeding: Breastfeeding is contraindicated while using flibanserin, as it is not known if the drug passes into breast milk and the potential risks to the nursing infant are not fully understood.

These additional contraindications in the Canadian labeling provide important information for healthcare providers and patients to ensure safe and appropriate use of flibanserin in Canada.

Warnings and precautions

CNS depression:

Flibanserin can make you feel drowsy or less alert, which might affect your ability to think clearly or do physical tasks.
It's important to be careful when doing things like driving or using heavy machinery after taking flibanserin.
Wait at least 6 hours before doing tasks that need you to be alert.
The risk of feeling drowsy is higher if you take flibanserin during the day, have liver problems, or use alcohol, other drugs that make you drowsy, or medications that boost flibanserin levels in your body, like some antibiotics or antidepressants.

Syncope and hypotension:

Taking flibanserin might lead to low blood pressure and fainting, especially if it's taken during the day or if you take more than the recommended dose.
If you're prone to low blood pressure, be extra cautious.
If you feel like you might faint, lie down right away, and if the feeling doesn't go away, seek medical help.
If you do faint, get medical attention promptly.
It's crucial to be aware of these risks and take necessary precautions while using flibanserin.

Hepatic impairment: [US-Boxed Warning]

For individuals with liver problems, it's important to note that using flibanserin can lead to higher levels of the medication in the body.
This increases the risk of experiencing severe low blood pressure and fainting.
Due to this heightened risk, the use of flibanserin is not recommended for individuals with hepatic impairment.
It's crucial to avoid using flibanserin if you have liver issues to prevent potentially dangerous side effects.

Flibanserin: Drug Interaction

Risk Factor C (Monitor therapy)
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Brentuximab Vedotin	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased.
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Bromopride	May enhance the CNS depressant effect of CNS Depressants.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
Celiprolol	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
CYP2C19 Inhibitors (Moderate)	May increase the serum concentration of Flibanserin.
CYP3A4 Inhibitors (Weak)	May increase the serum concentration of Flibanserin.
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Digoxin	Flibanserin may increase the serum concentration of Digoxin.
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Doxylamine	May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Estrogen Derivatives (Contraceptive)	May increase the serum concentration of Flibanserin.
Everolimus	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus.
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
HydrOXYzine	May enhance the CNS depressant effect of CNS Depressants.
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Larotrectinib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib.
Lofexidine	May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Mirtazapine	CNS Depressants may enhance the CNS depressant effect of Mirtazapine.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Naldemedine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine.
Naloxegol	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
P-glycoprotein/ABCB1 Substrates	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Loperamide.
Piribedil	CNS Depressants may enhance the CNS depressant effect of Piribedil.
Pramipexole	CNS Depressants may enhance the sedative effect of Pramipexole.
Progestins (Contraceptive)	May increase the serum concentration of Flibanserin.
Prucalopride	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride.
Ranolazine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine.
RifAXIMin	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin.
ROPINIRole	CNS Depressants may enhance the sedative effect of ROPINIRole.
Rotigotine	CNS Depressants may enhance the sedative effect of Rotigotine.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Selective Serotonin Reuptake Inhibitors	CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Silodosin	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin.
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Talazoparib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs.
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Risk Factor D (Consider therapy modification)
Afatinib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib.
Betrixaban	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor.
Bilastine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors.
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
Buprenorphine	CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants.
Chlormethiazole	May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
Colchicine	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details.
Dabigatran Etexilate	P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling.
DOXOrubicin (Conventional)	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided.
Droperidol	May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Edoxaban	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation.
Flunitrazepam	CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.
Opioid Agonists	CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
OxyCODONE	CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Perampanel	May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
Pitolisant	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant.
Sodium Oxybate	May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Suvorexant	CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Venetoclax	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors.
Zolpidem	CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.
Risk Factor X (Avoid combination)
Alcohol (Ethyl)	May enhance the hypotensive effect of Flibanserin.
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of Flibanserin.
CYP3A4 Inducers (Strong)	May decrease the serum concentration of Flibanserin.
CYP3A4 Inhibitors (Moderate)	May increase the serum concentration of Flibanserin.
CYP3A4 Inhibitors (Strong)	May increase the serum concentration of Flibanserin.
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
PAZOPanib	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.
Topotecan	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan.
VinCRIStine (Liposomal)	P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal).

Monitoring parameters:

Watch for Signs of Low Blood Pressure and Fainting

Keep an eye out for symptoms like dizziness, feeling lightheaded, or fainting.
If you feel like you might faint, lie down immediately.
Seek medical help if symptoms don't go away or if you faint.
It's important to be cautious and aware of these signs while using flibanserin to stay safe.

How to administer Flibanserin (Addyi)?

Take Once Daily at Bedtime

Administer the medication orally.
Take it only once a day.
Take it before going to bed at night.
Following this guidance helps ensure consistent and effective use of the medication.

Mechanism of action of Flibanserin (Addyi):

The exact way flibanserin works to treat hypoactive sexual desire disorder in premenopausal women is not fully understood.
However, it is believed to affect certain neurotransmitters in the brain.
Flibanserin acts as an agonist (activator) at some serotonin (5-HT) receptors and as an antagonist (blocker) at others.
Specifically, it activates certain types of serotonin receptors while blocking others, and it also blocks dopamine receptors to some extent.
This complex interaction with neurotransmitter receptors is thought to play a role in increasing sexual desire in women with hypoactive sexual desire disorder.

Protein Binding:

Approximately 98% of flibanserin binds primarily to albumin in the blood.

Metabolism:

Flibanserin is mainly broken down by enzymes called CYP3A4, with a smaller amount being metabolized by CYP2C19.
These enzymes convert flibanserin into inactive forms.

Bioavailability:

When taken by mouth, about 33% of the flibanserin dose is absorbed into the bloodstream.

Half-life Elimination:

The time it takes for half of the flibanserin in the body to be eliminated is roughly 11 hours.
In individuals with mild liver impairment, this half-life is extended to about 26 hours.
People who are poor metabolizers of CYP2C19 have a half-life of around 13.5 hours, compared to around 11 hours for extensive metabolizers of CYP2C19.

Time to Peak: